John Trojanowski, 75, a Giant in the Field of Neuropathology
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Scientists the world over are shocked and saddened to learn that John Q. Trojanowski passed away on February 8, at the altogether too-young age of 75. The cheerful and unmovable object to the unstoppable force that is his wife and lifelong research partner, Virginia Lee, Trojanowski was a rockstar in the field of neurodegeneration.
Sometimes likened to Mick Jagger (can you see the resemblance?), Trojanowski was a neuropathologist by training. He studied protein aggregates in brain tissue that would be identified as neurofibrillary tangles, α-synuclein Lewy bodies, and fibrils of TDP-43. Trojanowski championed the concept of pathological heterogeneity in neurodegenerative disease. He urged audiences at conferences and on Alzforum to recognize that nearly every other person with Alzheimer’s disease also has Lewy bodies in their brain, years before this idea was widely accepted by the field (see Oct 2003 Alzforum webinar). Trojanowski’s flamboyant style, warmth, and ready laugh were beloved; his stamina for asking probing questions at meetings—the stuff of legend.
John Trojanowski was a wonderful leader, wrote Bradley Hyman, Massachusetts General Hospital, Charlestown. “His style was to always push the field to the next level, whether that was in classic neuropathology and immunostaining or in drug discovery. His standing at the microphone at every ADRC directors meeting—jacket slung over his shoulders, ready to challenge an assumption, support great science, or point out a potential problem—will surely be missed,” Hyman wrote (see tributes below).
Trojanowski was born in Bridgeport, Connecticut, in 1946, while his parents were en route to Maine from Florida. He kept on the move in his early career, studying at Erasmus University, Rotterdam, and at the University of Vienna after graduating from King’s College, Wilkes-Barre, Pennsylvania. Back in the U.S., Trojanowski earned an M.D. and Ph.D. from Tufts University, Medford, Massachusetts, in 1976, then landed a residency at MGH in Boston. There he met Lee, rumor has it, while both were barhopping. The two moved to the University of Pennsylvania in 1980 and never left.
A Celebration. Trojanowski on December 8, at a reception honoring his lifetime of research. [Courtesy of David Wolk, UPenn.]
Last year Trojanowski fell several times. One fall in mid-December left him paralyzed from the neck down and in his weakened state, bacterial and viral infections, though not COVID, took hold. Trojanowski died as he had worked and lived, with Lee by his side. He was not yet retired; and indeed was a co-author of 67 papers in 2021 and 2022.
Trojanowski’s work spanned the gamut of neuropathology, pathophysiology, protein chemistry, genetics, and biomarkers. With Lee, he co-directed the Center for Neurodegenerative Disease Research at UPenn, which became a catalyst for neurodegenerative disease research worldwide (Dec 2001 conference news). The center banked its first brain sample in 1985, and recently cataloged its 2,000th. He had been directing UPenn's Institute on Aging since 2002, and its Alzheimer’s Disease Research Center since 1991. With Les Shaw, he established the Alzheimer’s Disease Neuroimaging Initiative biomarker core in 2004.
Trojanowski may be best remembered for his studies on tau. With Ken Kosik, now at University of California, Santa Barbara, he and Lee helped identify the microtubule binding protein as the major component of paired helical fragments found in AD brain (Kosik et al., 1988). Soon after, he helped elucidate the importance of tau hyperphosphorylation in tangle pathology (Masto et al., 1994; Garver et al., 1994). He reported one of the first transcriptomics studies of tangle-bearing hippocampal neurons (Ginsberg et al., 2000).
Trojanowski's interests extended beyond Alzheimer’s disease. Working with Gabor Kovacs, University Health Center, Toronto, and Günter Höglinger, German Center for Neurodegenerative Diseases, Munich, he identified different tau stages in progressive supranuclear palsy, a primary tauopathy (Kovacs et al., 2020).
Early Days. John with Virginia and Eddie Lee.
Other proteins and proteinopathies also intrigued Trojanowski. Manuela Neumann in his lab discovered that the ubiquitinated protein found in inclusions in both FTD and ALS was none other than TDP-43, showing this was a common pathology in both diseases (Oct 2006 news). In collaboration with Peter Nelson at the University of Kentucky, Lexington, Dennis Dickson at the Mayo Clinic, Jacksonville, Florida, and others, he introduced the concept of LATE, aka limbic-predominant age-related TDP-43 encephalopathy (May 2019 news). Just last year, researchers in his lab reported that LATE as a comorbidity in Lewy body disease spreads differently than when it occurs together with AD pathology (Uemura et al., 2022). Today, the NIA virtual workshop LATE 2022 began with a moment of silence in honor of Trojanowski.
Less well-known than his work on tau and TDP-43 is his work on Aβ. Yes, John Trojanowksi studied Aβ. This self-professed tauist was quite at ease with holding multiple, ostensibly competing hypotheses in his mind. He jokingly bemoaned Alzheimer's conferences as being "Aβ lovefests!," yet was actively curious about this peptide, too (e.g., Arai et al, 1991; Clark et al., 2003; Riad et al., 2020).
Trojanowski’s accomplishments would make for a long list. For example, he did important work on α-synuclein and vascular pathology. He was convinced of the importance of grappling with the neuropathological heterogeneity of neurodegenerative disease, and tried to define how combined pathologies shape the course of disease (Cornblath et al., 2020).
Early on, he recognized, and publicly promoted, the importance of exercise in staving off dementia (e.g. watch this You Tube video). Trojanowski could often be spotted in the hotel gym at the crack of dawn, and he rode his bike to work, daily.
Trojanowski won numerous awards and accolades, including the Potamkin Prize for research into AD and related disorders, which he shared with Lee and Michel Goedert, MRC Laboratory for Molecular Biology, Cambridge, U.K., in 1998.
Trojanowski was provocative, forthright, and challenging in his comments on the issues, noted Shaw. “He was a mentor and a major figure, scientifically, in my life in those days, and promoted my career, as he did for so many scientists he worked with. He came committed to helping, deepening, and widening our understanding of the disease process, how to detect it, and how to relate it to the definitive diagnosis, i.e. autopsy,” Shaw told Alzforum.
Despite his pre-eminence in the field, Trojanowski was approachable, always taking time for colleagues, students, and yes, reporters. Gregory Jicha, University of Kentucky, remembers shaking in his boots when he first met Trojanowski as a college student in 1988, but Trojanowski’s enthusiasm and advice soon led to collaborations. “In his honor, I can only hope to emulate his energetic engagement, sage guidance, and encouragement for our junior colleagues who will continue to move the field forward. This is John’s legacy. One that I know he was most proud of,” wrote Jicha.
“The ADNI team will remember John for his passion for science, and for reminding us that cognitive decline and dementia are caused by more than plaques and tangles, and in this he was obviously prophetic,” wrote Mike Weiner, University of California, San Francisco.
Did you know John Trojanowski? Did you laugh with him? Did you tussle with him? Or host this intrepid traveler as a guest speaker or collaborator at your institution? Share an anecdote, a memory, a picture to help us build a tribute by the global neurodegeneration research community for a life well-lived.—Tom Fagan and Gabrielle Strobel
References
Webinar Citations
News Citations
- CNDR 2nd Annual Retreat: Welcome and Introduction
- New Ubiquitinated Inclusion Body Protein Identified
- Introducing LATE—A Common TDP-43 Proteinopathy that Strikes After 80
Paper Citations
- Kosik KS, Orecchio LD, Binder L, Trojanowski JQ, Lee VM, Lee G. Epitopes that span the tau molecule are shared with paired helical filaments. Neuron. 1988 Nov;1(9):817-25. PubMed.
- Matsuo ES, Shin RW, Billingsley ML, Van deVoorde A, O'Connor M, Trojanowski JQ, Lee VM. Biopsy-derived adult human brain tau is phosphorylated at many of the same sites as Alzheimer's disease paired helical filament tau. Neuron. 1994 Oct;13(4):989-1002. PubMed.
- Garver TD, Harris KA, Lehman RA, Lee VM, Trojanowski JQ, Billingsley ML. Tau phosphorylation in human, primate, and rat brain: evidence that a pool of tau is highly phosphorylated in vivo and is rapidly dephosphorylated in vitro. J Neurochem. 1994 Dec;63(6):2279-87. PubMed.
- Ginsberg SD, Hemby SE, Lee VM, Eberwine JH, Trojanowski JQ. Expression profile of transcripts in Alzheimer's disease tangle-bearing CA1 neurons. Ann Neurol. 2000 Jul;48(1):77-87. PubMed.
- Kovacs GG, Lukic MJ, Irwin DJ, Arzberger T, Respondek G, Lee EB, Coughlin D, Giese A, Grossman M, Kurz C, McMillan CT, Gelpi E, Compta Y, van Swieten JC, Laat LD, Troakes C, Al-Sarraj S, Robinson JL, Roeber S, Xie SX, Lee VM, Trojanowski JQ, Höglinger GU. Distribution patterns of tau pathology in progressive supranuclear palsy. Acta Neuropathol. 2020 Aug;140(2):99-119. Epub 2020 May 7 PubMed.
- Uemura MT, Robinson JL, Cousins KA, Tropea TF, Kargilis DC, McBride JD, Suh E, Xie SX, Xu Y, Porta S, Uemura N, Van Deerlin VM, Wolk DA, Irwin DJ, Brunden KR, Lee VM, Lee EB, Trojanowski JQ. Distinct characteristics of limbic-predominant age-related TDP-43 encephalopathy in Lewy body disease. Acta Neuropathol. 2022 Jan;143(1):15-31. Epub 2021 Dec 2 PubMed.
- Arai H, Lee VM, Messinger ML, Greenberg BD, Lowery DE, Trojanowski JQ. Expression patterns of beta-amyloid precursor protein (beta-APP) in neural and nonneural human tissues from Alzheimer's disease and control subjects. Ann Neurol. 1991 Nov;30(5):686-93. PubMed.
- Clark CM, Xie S, Chittams J, Ewbank D, Peskind E, Galasko D, Morris JC, McKeel DW Jr, Farlow M, Weitlauf SL, Quinn J, Kaye J, Knopman D, Arai H, Doody RS, DeCarli C, Leight S, Lee VM, Trojanowski JQ. Cerebrospinal fluid tau and beta-amyloid: how well do these biomarkers reflect autopsy-confirmed dementia diagnoses?. Arch Neurol. 2003 Dec;60(12):1696-702. PubMed.
- Riad A, Lengyel-Zhand Z, Zeng C, Weng CC, Lee VM, Trojanowski JQ, Mach RH. The Sigma-2 Receptor/TMEM97, PGRMC1, and LDL Receptor Complex Are Responsible for the Cellular Uptake of Aβ42 and Its Protein Aggregates. Mol Neurobiol. 2020 Sep;57(9):3803-3813. Epub 2020 Jun 23 PubMed.
- Cornblath EJ, Robinson JL, Irwin DJ, Lee EB, Lee VM, Trojanowski JQ, Bassett DS. Defining and predicting transdiagnostic categories of neurodegenerative disease. Nat Biomed Eng. 2020 Aug;4(8):787-800. Epub 2020 Aug 3 PubMed.
External Citations
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Comments
retired from NIH/NIA
I was so sorry to hear of John’s demise. I first met John and Virginia around 35 years ago at an NIH research grant review site visit I led to the University of Pennsylvania. From that first meeting, I knew there was something special about the two of them individually, and the team approach they took to research. John, with his clinical and neuropathology background, and Virginia, with her molecular orientation, complemented each other.
They challenged each other all the time, sometimes loudly and in public. I looked forward to our many interactions, both scientific and personal. We attended many meetings, shared many meals together and inevitably, the two of them would get into a debate, and I sat and back enjoyed the way they played off each other. It was always obvious that they respected each other and were trying to advance science with their spirited arguments.
John was a great teacher and mentored many trainees, many of whom have also made significant contributions to neurodegenerative research. John's legacy is the outstanding science that continually streams from the scientists he trained and from the laboratories and centers that he created and supervised up until the end.
Washington University School of Medicine
A neuropathologist by training, John Q. Trojanowski (JQT), was a towering figure in neurodegeneration research for over four decades. In close collaboration with his partner and wife Virginia Lee, Ph.D., and among many other major contributions to the understanding of neurodegenerative diseases, John contributed mightily to the characterization of tau and its isoforms (and was a proud and loud “tauist” for many years.
John established the role of α-synuclein in Alzheimer's disease and the Lewy body disorders, and basically identified TDP-43 proteinopathy in frontotemporal lobar degeneration, amyotrophic sclerosis, and Alzheimer's disease. He was a champion for examining the pathophysiological spectrum of neurodegenerative dementing disorders, rather than limiting the focus to amyloid plaques and neurofibrillary tangles.
In almost any setting, he could be counted on to unreservedly voice his opinion on a wide variety of matters, from NIA funding priorities to ADRC-wide or ADNI-wide initiatives to a discussion of the new research discoveries.
He was passionate about science, and his passion drew people to him. He trained and mentored many leading neuropathologists and neuroscientists, in the U.S. and globally, who all remain very loyal to both John and Virginia.
He was the founding director of the NIA-funded Alzheimer Disease Center at Penn, and I had the honor of serving as chair of the Penn ADC’s External Advisory Committee for two decades. In doing so I became close with both John and Virginia, which has been entirely to my benefit. One of the great pleasures of interacting with John and Virginia was to be an awed observer of their not infrequent and often highly animated disagreements! The neurodegeneration research field has lost a giant in John Trojanowski, and we all miss our great friend.
UCSF
John and his wife, Virginia were highly accomplished investigators in the Alzheimer’s field long before I entered it. In 2002, as we were planning for the Alzheimer’s Disease Neuroimaging Initiative (ADNI), Leon Thal insisted that John lead its Biomarker Core. When we started writing the ADNI grant, John added Les Shaw from UPenn’s Department of Laboratory Medicine as Co-PI of the Biomarker Core. I remember a wonderful dinner at a Chinese restaurant in Philadelphia’s Chinatown with John, Virginia, Les, and other ADNI Core leaders just as ADNI was getting started.
John had amazing energy and passion for science. He seemed to be working all the time, and I often urged him to get some sleep. He was particularly passionate about the multifactorial causes of dementia, and the importance of α-synuclein, TDP 43, cerebrovascular disease, and other pathologies as causes of, and contributors to, cognitive decline and dementia.
John, together with the UPenn ADRC, built a world-famous brain bank together with CSF aliquots, which were used for many assay validation and exploratory studies leading to important discoveries. John and Virginia are particularly known for their pioneering work demonstrating that TDP-43 plays an important role in cognitive decline and dementia, often mimicking the amnestic symptoms commonly associated with plaques and tangles, especially in the older old.
I know that John particularly looked forward to vacation trips to the Caribbean. This was the one time of the year when he seemed to stop communicating by email and had a chance to get away from work.
Aside from his amazing scientific contributions, John inspired generations of medical investigators including pathologists, neurologists, psychologists, and biochemists. For example, Dan Skovronsky, now at Lilly, trained as a neuropathologist with John and Virginia, and then went on to found AVID, which developed Florbetapir, the amyloid PET tracer. Many hundreds of investigators have been inspired, influenced, or directly trained by John.
The ADNI team will remember John for his passion for science, and for reminding us that cognitive decline and dementia are caused by more than plaques and tangles, and in this he was obviously prophetic.
Our condolences to Virginia. We will miss our good friend.
Sanders-Brown Center on Aging
I first met John in 1988 at a Society for Neuroscience meeting, where I was presenting a poster on my work in an animal model of Parkinson’s disease. I was an undergraduate at the time. His enthusiasm and sage advice were welcome as I was shaking in my boots, recognizing his name and pre-eminence in the field. John cultivated my entire career from undergraduate through my M.D. and Ph.D. training, through residency and academic progress to full professor.
Over the 32+ years of interaction with John, he became a friend and served as one of the most exemplary role models I have had in my career. We have collaborated on many projects, and he welcomed scientists at all levels with open arms and fruitful collaborations.
His passing is a great loss for the field of degenerative dementia, spanning both dementia and movement disorders. In his honor, I can only hope to emulate his energetic engagement, sage guidance, and encouragement for our junior colleagues who will continue to move the field forward. This is John’s legacy. One that I know he was most proud of.
New York Institute for Basic Research in Developmental Disabilities
It is hard to believe that John has passed away. John was a highly accomplished neurodegenerative diseases researcher. His work covered a wide area of research, which included neuropathology and pathophysiology of not only Alzheimer's disease but also tauopathies and Parkinson's disease.
He was an active discussant at scientific meetings. He was a happy person and had a great sense of humor. Several years ago, at an AD/PD meeting in Torino, John was chairing a session and a scientist presenter from Israel could not direct the laser point to the screen and instead kept pointing it in John's eyes. After a couple of gentle reminders to the gentleman, John told him that he would take away the laser pointer from him if he did not stop pointing it in his eyes, which made the whole audience laugh. That was John!
I will miss him. His death is a truly great loss to the scientific community, especially the Alzheimer's research community.
John Trojanowski was a wonderful leader, encouraging students and trainees who are scattered across the country and now leaders themselves. His style was to always push the field to the next level, whether that was in classic neuropathology and immunostaining, or in drug discovery.
His pivotal role, with Virginia, of course, in defining, elaborating, and understanding tau biology led to fundamental discoveries and insights that are central to the field. A true “rock star,” he used his stature to support his colleagues at Penn, contribute to national and international neurodegeneration efforts, and be a wonderful voice of reason in all discussions.
His standing at the microphone at every ADRC directors meeting—jacket slung over his shoulders, ready to challenge an assumption, support great science, or point out a potential problem—will surely be missed. I will personally miss him enormously.
Stanford University
My sincerest sympathies go to Virginia. She and John were an amazing team, personally and professionally, inspiring generations of neuroscientists. I am sure others will reflect on John’s genius, multiple field-changing discoveries, and commitment to aging research.
I add to this impressive list of achievements his generosity. John gave freely of his time and expertise not only to his many trainees but to anyone who shared his vision of a better future for people suffering with neurodegenerative diseases. Through his remarkable generosity, many of us have stood on his shoulders, and his impact is in fact much greater than the seminal discoveries and innovations made by the Lee/Trojanowski laboratory.
University of Pennsylvania
John was an inspirational scientist, a caring mentor, and a wonderful friend. I’m sure that many people feel similarly, and John will be sorely missed.
We first met when I was a resident in neurology and I wanted to learn about the neuropathology of neurodegenerative diseases. This was in 1988. I was extraordinarily naive, but John patiently mentored me.
Our first publication together was in 1995, when I had a patient with “progressive non-fluent aphasia” (now called the non-fluent/agrammatic variant of primary progressive aphasia) who had passed and donated her brain to the Penn Center for Neurodegenerative Disease Research (CNDR) Brain Bank led by John and his lifetime partner, Virginia Lee. I had just published a clinical series of these cases, and I was curious about the pathologic basis for this unusual clinical presentation. This patient had Pick’s disease, and this may have been one of the first applications of tau antibody to diagnose Pick’s disease in humans.
Since then, we’ve published many papers and worked on many grants together, and I've always found it a joy to work with John. I learned so much from him—not just in terms of content, but how to ask the correct scientific questions.
Over the years, John was a wonderful friend and guide who helped me in so many personal ways. I will be forever indebted to John, and I only hope that I can serve as an equally good mentor and friend to others and in the manner inspired by John.
MRC Laboratory of Molecular Biology
University of Cambridge
John Trojanowski was a giant of research on neurodegenerative diseases, and a special friend. He was one of only a handful of scientists at the forefront of research on Alzheimer’s disease (AD) and other tauopathies, Parkinson’s disease (PD) and other synucleinopathies, as well as amyotrophic lateral sclerosis (ALS) and other TDP-43 proteinopathies.
Tau protein was identified as an integral component of the paired helical filament (PHF) of AD in the mid-late 1980s (for a review, see Lee et al., 2001). However, the insolubility of filaments isolated from tangle fragments made it difficult to exclude the possibility that proteins other than tau were also present. Quantitative analysis was virtually impossible. John and colleagues used a method for extracting more soluble filaments to show that these dispersed PHFs were only made of tau (Lee et al., 1991). Tau is now known to be the most commonly misfolded protein in neurodegenerative diseases, and there are many tauopathies besides AD.
John Trojanowski, Virginia Lee, and Michel Goedert at the Alzheimer 100 Centennial conference in Tuebingen, Germany. See https://www.alzforum.org/news/conference-coverage/alzheimer-100-centennial.
In recent years, John and colleagues have also made important contributions to the expanding field of the prion-like behaviour of tau and other assemblies (for a review, see Uemura et al., 2020). Work on the enhancement of seeded tau aggregation by Aβ plaques has been particularly intriguing (He et al., 2018).
February 1991–June 1998 was not the best of times for working on tau in relation to neurodegeneration. During this period, the sessions on tau moved progressively toward the final day of scientific meetings, when most people had already left. One was largely preaching to the small band of other believers. Religious sects must be like that!
During those meetings, John, Virginia and one of us (M.G.) met in our respective rooms to complain and commiserate, while drinking copious amounts of beer from the hotel minibars. These gatherings created a special bond between us that transcended the fact that we were also competitors. We had the best of times together, one of the last occasions being a convivial dinner, followed by some late-night sightseeing, in London during AAIC 2017.
It was toward the end of the 1991–1998 period that we published our most influential collaborative work. This was not on tau, but on the presence of α-synuclein in the Lewy pathology of Parkinson’s disease and dementia with Lewy bodies (Spillantini et al., 1997).
The following year, John, Virginia, and colleagues (Tu et al., 1998), alongside others (Wakabayashi et al., 1998; Spillantini et al., 1998) reported that multiple-system atrophy is also a synucleinopathy. Following on from this work, which was mostly on human brain, they showed that α-synuclein assembly spreads through the mammalian brain (Luk et al., 2012) and that different conformers of assembled α-synuclein may underlie Lewy body diseases and multiple-system atrophy (Peng et al., 2018).
These findings left the ubiquitinated inclusions of ALS and some forms of frontotemporal lobar degeneration unaccounted for in terms of knowing their major components. John and Virginia used a combination of immunology and protein chemistry to show that TAR DNA-binding protein-43 (TDP-43) is that major component (Neumann et al., 2006). This important work opened a whole new chapter. TDP-43 inclusions are now known to be among those most commonly found in age-related neurodegenerative diseases.
John Trojanowski and Virginia Lee were not only partners in life, but their scientific work was also inextricably linked. We recall a fellow scientist who was surprised to learn that John and Virginia were two different people. He thought John’s name was: Lee Trojanowski. Little did he know! In science it is often important to be able to bounce ideas off others, and some of the discussions between John and Virginia are the stuff of legend; their areas of expertise were beautifully complementary. John and Virginia are an example of the whole being much more than the sum of its parts.
References:
He Z, Guo JL, McBride JD, Narasimhan S, Kim H, Changolkar L, Zhang B, Gathagan RJ, Yue C, Dengler C, Stieber A, Nitla M, Coulter DA, Abel T, Brunden KR, Trojanowski JQ, Lee VM. Amyloid-β plaques enhance Alzheimer's brain tau-seeded pathologies by facilitating neuritic plaque tau aggregation. Nat Med. 2018 Jan;24(1):29-38. Epub 2017 Dec 4 PubMed.
Lee VM, Balin BJ, Otvos L, Trojanowski JQ. A68: a major subunit of paired helical filaments and derivatized forms of normal Tau. Science. 1991 Feb 8;251(4994):675-8. PubMed.
Lee VM, Goedert M, Trojanowski JQ. Neurodegenerative tauopathies. Annu Rev Neurosci. 2001;24:1121-59. PubMed.
Luk KC, Kehm V, Carroll J, Zhang B, O'Brien P, Trojanowski JQ, Lee VM. Pathological α-synuclein transmission initiates Parkinson-like neurodegeneration in nontransgenic mice. Science. 2012 Nov 16;338(6109):949-53. PubMed.
Neumann M, Sampathu DM, Kwong LK, Truax AC, Micsenyi MC, Chou TT, Bruce J, Schuck T, Grossman M, Clark CM, McCluskey LF, Miller BL, Masliah E, Mackenzie IR, Feldman H, Feiden W, Kretzschmar HA, Trojanowski JQ, Lee VM. Ubiquitinated TDP-43 in frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Science. 2006 Oct 6;314(5796):130-3. PubMed.
Peng C, Gathagan RJ, Covell DJ, Medellin C, Stieber A, Robinson JL, Zhang B, Pitkin RM, Olufemi MF, Luk KC, Trojanowski JQ, Lee VM. Cellular milieu imparts distinct pathological α-synuclein strains in α-synucleinopathies. Nature. 2018 May;557(7706):558-563. Epub 2018 May 9 PubMed.
Spillantini MG, Schmidt ML, Lee VM, Trojanowski JQ, Jakes R, Goedert M. Alpha-synuclein in Lewy bodies. Nature. 1997 Aug 28;388(6645):839-40. PubMed.
Spillantini MG, Crowther RA, Jakes R, Cairns NJ, Lantos PL, Goedert M. Filamentous alpha-synuclein inclusions link multiple system atrophy with Parkinson's disease and dementia with Lewy bodies. Neurosci Lett. 1998 Jul 31;251(3):205-8. PubMed.
Tu PH, Galvin JE, Baba M, Giasson B, Tomita T, Leight S, Nakajo S, Iwatsubo T, Trojanowski JQ, Lee VM. Glial cytoplasmic inclusions in white matter oligodendrocytes of multiple system atrophy brains contain insoluble alpha-synuclein. Ann Neurol. 1998 Sep;44(3):415-22. PubMed.
Uemura N, Uemura MT, Luk KC, Lee VM, Trojanowski JQ. Cell-to-Cell Transmission of Tau and α-Synuclein. Trends Mol Med. 2020 Oct;26(10):936-952. Epub 2020 May 1 PubMed.
Wakabayashi K, Yoshimoto M, Tsuji S, Takahashi H. Alpha-synuclein immunoreactivity in glial cytoplasmic inclusions in multiple system atrophy. Neurosci Lett. 1998 Jun 19;249(2-3):180-2. PubMed.
Co-Director, Brigham and Women's Hospital's Ann Romney Center for Neurologic Diseases
I join many others who are mourning the tragic and untimely loss of a true leader in the field of neurodegenerative disease, John Trojanowski.
I recall first meeting John on one of his trips across town to visit Virginia at Mike Shelanski’s lab at Children’s Hospital. Virginia and I were postdocs together and pipetted at adjacent benches; John was training in neuropathology at Massachusetts General Hospital. I remember that John immediately impressed me with his warm, engaging, and urbane persona. In those early days, and from time to time throughout John’s distinguished career, he and I had a lot of fun discussing and debating broad themes in human neurobiology and the nuances of basic and translational research on brain diseases.
John had a deep knowledge of neuropathology and the molecular mechanisms of age-related nervous system disease, and he was not afraid to use it in discourse and debate. While I found myself in agreement with John on many topics, we also found opportunities to debate aspects of pathogenesis, and his keen mind and articulate delivery made John a formidable sparring partner. A topic we sometimes disagreed on was the respective roles of amyloid and tau accumulation in the early development of Alzheimer’s disease. My recollection is that we came quite close to a shared view of AD mechanisms but agreed to disagree on some points. Regardless of the earnestness we each brought to the debate, John was always incredibly gentlemanly. His wonderful sense of humor and collegiality endeared him to so many in the field.
One trait I suspect some of us recall is John’s ability to ask penetrating questions of a speaker. On occasion, the queries would come one after another, and he might not let up for a while. But this exercise always ended with far more light than fire, and listeners were much enriched by John’s innate facility with the Socratic method.
Of course, the defining feature of John’s career was his remarkably successful collaboration with Virginia over more than four decades. The complementarity of their distinct intellects and styles was on display at myriad conferences and academic visits around the globe. Forging such a highly productive and long-lasting partnership is unusual in science, and it is especially impressive between spouses. Lee and Trojanowski, Trojanowski and Lee: These two created a wealth of discoveries and insights that continue to lead us toward a deeper understanding of neurodegeneration.
I have no doubt that Virginia will carry on their tradition, but for her, and for all of us who called John a friend, we will sorely miss his unique contribution. Thank you, John, for all you have meant to us and to our field.
UC San Francisco
I first met John Trojanowski and his partner, Virginia Lee, in the late 1990s, at a meeting in Philadelphia. John and Virginia were already dementia royalty, having made seminal observations around the role of tau in Alzheimer’s disease and frontotemporal dementia and α-synuclein in Parkinson’s disease. Soon afterward, John and Virginia characterized the non-tau protein that aggregated in one-half of FTD cases and in most of the cases of ALS, TDP-43.
John was encyclopedic regarding the neuropathological features of neurodegenerative disorders. He not only codified modern neuropathology, he performed the research that changed the field. I looked forward to every paper that would come from John and Virginia!
John had an incredible zeal for science, culture, and life. He and Virginia traveled the world as ambassadors for science and for their beloved University of Pennsylvania. He was a relentlessly curious man who lived every moment of his life with passion.
I am eternally grateful to John and Virginia for their support of my work, and John served as the neuropathologist on my program project grant, “frontotemporal dementia, genes, images and emotions.” I feel lucky to have known John, a towering presence in neuroscience and a magnificent mentor, investigator, and figure in Alzheimer’s disease and related disorders.
Everyone I have spoken with about John’s death speaks of the shock and sadness of losing someone like John, a person whose science was so critical for the underpinnings of our scientific and our personal worlds.
University of Tübingen and DZNE AG Neumann
John has been one of my heroes ever since I began my training in neuropathology in the late '90s. I first met John in person at the AANP meeting in Denver in 2002. I had just delivered my first talk at an international congress and was not quite happy with how I had responded to some questions, when John approached me with his typical enthusiasm to congratulate and to tell me how he enjoyed reading my paper. Then, in 2005, when John and Virginia gave me the opportunity to work in their lab on my favorite project on frontotemporal dementias, which eventually led to the identification of TDP-43, it was a dream come true.
Working with John and Virginia was a real turning point in my professional life, as it has been for so many other scientists. John was a caring mentor, a fantastic teacher, a great leader, always energetic, enthusiastic, and most importantly, not only a brilliant scientist, but also a fascinating, remarkable, and generous human being.
He will be dearly missed.
University of Paris VI
John was an inspiring model for us. He contributed important discoveries with his wife, Virginia. He made them possible by devising research strategies consisting of a systematic exploration of pathology using the most advanced technology.
We had the pleasure of seeing him regularly during his visits to Paris, where he came with Virginia. We then had the opportunity to compare the difficulties met in the development of neuropathology encountered in Europe with those of the United States.
John was a kind, intelligent, and very cultured man. It was always a great pleasure to share with him the progress of research, to express our hopes and disappointments. We shall deeply miss him, and so will neuropathology.
Johns Hopkins University
I’m just one of hundreds, perhaps thousands, whom John and Virginia influenced by example and by mentoring. They seriously helped launch my career as inspirational collaborators. We first met in the late 1980s, while I was working at Upjohn, and struck up a lasting friendship that I will always treasure. There are many stories which I’ll hold back now, best left for receptions or after-meeting drinks at conferences. But I’d like to share the following, because it exemplifies so well what others are saying.
Background: I had the privilege of chairing the NIA committee that crafted the recommendations for future ADRC strategies between 2015 and 2017. When those recommendations were near completion, the committee convened on the NIH campus for our final in-person discussions on Thursday–Friday, March 9–10, 2017. In preparation for submitting the recommendations to the NIA Council in May, the second day included a teleconference to which all ADRC directors were invited for discussion and comment with the committee and NIA leadership on the draft recommendations, which had been previously shared with them.
I led that meeting, flanked on my left by Nina Silverberg, and on my right by Richard Hodes, with about 40 other people around the large table. During the development of those recommendations, there had been tension related to the neuropathology cores about the number of brains being archived in hundreds of freezers across the ADRCs, and whether continued accrual, or even retaining the brains currently in freezers, was appropriate. The counterpoint was to make space by disposing of “old brains” and focusing on early stage autopsies, CDR 0 - 1. As might be expected, John had an opinion on this. There was a transcript made of that two-day meeting, which I managed to find this morning. I’d like to share the excerpt from that transcript containing some of John’s comments, and a vignette of his humor. Here is a real-time sample of John’s presence, insights, and challenges in a meeting discussion, cut-and-pasted from that transcript. It’s John speaking here. The overarching message is an example of what John always managed to convey: “Be prepared to look for what we can’t conceive asking, based on what we know today.”
"DR. TROJANOWSKI: We did send in a statement that reflected our center's collective thoughts on the excellent recommendations. ... In our written comments, we didn't intend to critique or make a comment on all of the recommendations. There was a discussion of harmonizing among the centers, how they work in various areas, and we think that's important. But we also think diversity of the centers is extremely important that they each can bring a different focus, a perspective, to Alzheimer's Disease and related dementias. We very much support the notion that centers should focus not just on Alzheimer's but also related dementias. I think those are my brief comments. ...
"DR. TROJANOWSKI: Nina, may I ask a question of Bud?
"DR. SILVERBERG: Sure.
"DR. TROJANOWSKI: So, Bud, we're undertaking an effort now in our autopsy brain program, about 1600 brains, to go back and backfill—
"DR. SILVERBERG: John, there's a lot of background noise on your phone and it's hard to hear you.
"DR. TROJANOWSKI: I don't know how to mute my phone while I'm talking. (Laughter). ... So the question is we are backfilling data on autopsies, data such as TDP-43 and α-synuclein. As you know, they were discovered well after the Centers were instituted. And it would be very valuable, we think, to be able to draw upon our autopsy data from before the TDP-43 discovery and α-synuclein. And we have some resources to do it. But the question is would it enrich the entire NACC database for all centers to do this? And are there resources that could be applied to do this so that you could go back to 1985 and have TDP-43 data and synuclein data on all of the autopsies that are in NACC?
"DR. KUKULL: It would be terrific. We don't have any money to do it. What it would involve would be having to do that, having to do all those immunohistochemistries I guess on your end and then probably just fill out the neuropathology on that.
"DR. TROJANOWSKI: That's exactly correct. Would that be valuable for the overall Alzheimer's Center consortium?
"DR. KUKULL: From my point of view, I think it would be great because then we'd be able to look back and see what a lot of these older data look like in terms of TDP-43 which we really don't have a good handle on the data we have now. I think it would open up a whole new line of research, really, of looking at these things more carefully against the clinical diagnoses that were assigned at the time.
"DR. TROJANOWSKI: And I know you don't have resources. So, Barry, my recommendation would be that I would suggest adding this recommendation to what is planned for the ADCs to backfill older cases with data of TDP-43 and synuclein to make the database much richer for mining.
"I made a summary statement later in that session, based on our appreciation for John’s recommendation: “It's not an either/or. We do need to have the early cases. They are hard to get. You know, the pre-symptomatic or the—and as John Morris suggested, that we have a need for CDR 0, 0.5, and 1.0—they are hard to get. We did not have the depth of knowledge we have today on atypical presentation, sub-types of the disease, FTD, the various genetic forms of FTD. We can go on with a list of examples like that ... if we threw brains away after we stored them for a year, we would not have the archived material to go back and ask what are the correlations between what we have learned in the past five years and the clinical presentations of these individuals who were noted at the time that they came to autopsy? So there is a value in having that archived tissue as the field develops clinically and with respect to new biomarkers. That is not to say that this is any more important than trying to accrue the early stage brains, but it is not the same as saying we have a lot of late-stage disease brains in our freezers, we don't need them, because when we're talking about atypical presentations in sub-types, we are talking about rare cases that are unique for reasons that we don't know yet."
John, we are so going to miss you.
University of Pennsylvania
John was a towering figure in our field. My first encounters with John were when I was a neurology resident at the University of Pennsylvania through our clinical-pathological conference (CPC) lectures, at which he frequently presented. At that point, I did not yet know his science, just that the Trojanowski/Lee lab was a powerhouse. My lasting memory of those CPCs was of a person who did his work with tremendous enthusiasm and wanted everyone else to share in this excitement.
That enthusiasm and joy around his work never left John, as he had the purest desire to learn all he could to advance the field of neurodegenerative disease research. It is worth pointing out that his curiosity extended well beyond his own work and even his area of research and science altogether. As director of Penn’s Institute on Aging, he moderated lectures and symposia that were sometimes relatively far removed from neurodegenerative disease, yet I was always astonished that he would still be fully engaged and manage to ask a probing set of questions at the end (and sometimes throughout) the presentation. John was like that for any topic, which made him such a pleasure in social contexts, as well. He was interested in learning about people, their backgrounds, and their passions.
I really got to know John better when I returned to Penn in 2008. I recall having an interview with this larger-than-life figure. Despite his significant height advantage, he sat on top of a stool in his office while I was in a lower chair; thus, making him literally larger than life for me! However, he could not have been more kind and interested in what work I had done and hoped to do at Penn. He exhibited his signature excitement in describing all the opportunities for collaboration and work at Penn—opportunities that stem from the amazing infrastructure he built during in his long career.
John built a milieu at Penn that integrated the work of investigators and clinicians from multiple disciplines and across neurodegenerative conditions. He was prescient to the notion that neurodegenerative disease is often mixed in pathology and shared mechanisms that are best tackled through collaborative, non-siloed investigations. Many scientists at Penn and elsewhere have built their careers leveraging this infrastructure, and John could not be more proud of this. Indeed, he took tremendous pride in the recruits he brought to Penn and the success of individuals within his centers. Personally, he was incredibly generous to me in supporting and cheerleading my career, for which I will always be deeply appreciative.
While much has been and will continue to be said about his science, which will surely be the foundation of work for decades ahead, one thing that became clear to me over these years, including through his recent illness, is the tremendous love and partnership he had with Virginia. They truly were linked in every aspect of their lives with infinite respect and affection. It is a model that we all can learn from and try to emulate in our own lives.
University of California, Santa Barbara
Nothing shakes one’s own sense of mortality more than the death of a contemporary. At a time when Tau was still new and shiny, and every day brought a new insight, a time when many of us were meeting each other for the first time at the starting gate of our careers, I visited John and Virginia in their lab at UPenn and their house in Center City.
They were a rarity in science, a team completely knit together. We knew so little then about the disease we studied (and probably know even less now), but their shared lab was abuzz with the promise of all the remarkable discoveries not yet made. The excitement in the lab was palpable as each gel was illuminated on the light box and each brain section came into focus on the multiheaded microscope. The hours raced by filled with animated conversation that I cannot even begin to recreate at this great distance in time. The words are gone but the persona remains, indelible.
“Life changes in the instant. The ordinary instant.”—Joan Didion, The Year of Magical Thinking
Mayo Clinic College of Medicine
I was saddened to learn of John’s passing, because he was a member with outsized influence of the extended family of dementia neuroscientists. John was always gracious and respectful of all. His exuberance for science and his thoughtfulness lit up the room, whether it was a meeting of a few or an auditorium of a thousand.
UT Southwestern Medical Center
I am deeply saddened to learn of John Trojanowski's passing. As a scientist, as a statesman for the field, he is irreplaceable. His work is foundational.
I share the following, not as a close acquaintance of John, but as a testament to his unescapable influence upon young trainees in the field. His presence was enormously positive and inspiring. He imparted a cinematic sheen to the scientific path.
In 2012, I was a lost graduate student, recovering from addictions past, holding a bit of a provocative data, the importance of which I lacked appreciation for. At my first conference, I presented the story (poorly), and was praised by a select few (whom I forget). What I won't forget, however, is the thoughtful challenges put forward by John and Virginia. This blossomed into several friendly arguments during the course of the conference. And of course, spirited debates at conferences since. At one point, John tried to mediate a less-friendly argument between a colleague and Virginia. His mediation skills were unrivaled. More importantly, he danced tirelessly. And science was beautiful. It hasn't been the same of late.
I will miss John Trojanowski greatly. But so will everyone else.
Stanford Neuropathology
I was fortunate to briefly work with JQT during my time as a trainee at Penn. As a young neuropathologist, I regarded John as one of my scientific heroes. He graciously provided career advice during meetings, where we would discuss topics ranging from future directions in neurodegeneration research to Goethe. My deepest sympathies to Virginia, and everyone who was lucky enough to know him.
https://www.kudoboard.com/boards/g4GnMiVk/jqtrojanowski
TrueBinding
It is hard to believe that the great John Trojanowski left this world. I still remember first meeting him and Dr. Virginia Lee at an SfN meeting, when I was doing my postdoc in Dr. Charlie Glabe's lab. John was a great researcher, and his ideas regarding Alzheimer's and other neurodegenerative diseases neuropathology were amazing. He was one of the discoverers of the role of TDP43 in tauopathies.
RIP. His death is a truly great loss to the Alzheimer's research community.
CureDementia Fund of The Philadelphia Foundation
Our hearts go out to Virginia on the loss of her beloved John, husband and partner in work and in life itself. They are both generous souls who did/do everything possible to advance CNDR. We will miss John, and we extend our deepest condolences to Virginia as she carries on the mission they have pursued all their lives.
—David Hoefner co-authored this tribute
University of the Saarland
Dear John, you were marvelous and very, very kind. Not to mention that you were a genius too. It was an honor and an experience to have made your acquaintance.
We will miss you.
University of Washington
I am profoundly saddened to hear of John's passing. I am quite sure he was the first neuropathologist I had ever met when I consulted with him in 1984 about how to go about immunolocalizing the p75 neurotrophin receptor in human brain. I vividly recall how warmly welcoming and helpful he was. Were he not a giant in the field of neurodegenerative disease, he still would be remembered for being such a wonderful person.
UCSF
I first met John and Virginia as a Penn undergrad in about 1984 or 1985. I worked in Virginia's lab as an undergrad and then later was her first Ph.D. student as an M.D./Ph.D. Working with one was working with both, and that was always the case. The two made such a potent team—John with his amazing and encyclopedic understanding of brain anatomy and neuropathology, and Virginia with her tremendous focus on the cell and molecular biology of the nervous system.
I continued to be occasionally in touch over the years even though I was in a quite different field. Most commonly I would hear from John to enlist my help in proposing that Virginia receive a scientific award—he was so dedicated to her and so focused on making sure that her tremendous contributions to the field be recognized. I am so sorry that John is gone and terribly sad for Virginia, who has lost her partner in life.
The University of Hong Kong
I join all my many friends in this field who are saddened to learn of John’s passing. We had the honor to have John and Virginia give Keynote talks at our International Alzheimer’s Disease Conference in Hong Kong in 2017. John was not just giving a talk in our conference. He gave lots of insights to us on AD research and linked us to his research on α-synuclein.
My postgraduate student was given a chance to study in their laboratory for three months. Since then, we have a collaboration on one project investigating the spreading of α-synuclein and neurodegeneration triggered by different stimuli. In that meeting, he tried to help Hong Kong scientists transfer some postmortem AD brains for research. John was a person who enthusiastically helped science and young investigators. While I feel sad to lose this remarkable scientist, I am sure Virginia and their lab will continue their contributions to the field of neurodegeneration.
University of Pennsylvania
Sitting for my medical school interview with Virginia M.-Y. Lee in the basement of the UPenn Maloney building, I was not doing well. Our discussion about amyloid and microglia left me utterly convinced that I knew nothing about neurodegenerative disease. Then a man cracked open the door and popped his head in to offer Virginia an apple. Virginia snapped, yelling at John to get out. At that moment, I was convinced I was not going to get into Penn. I had no idea what an influence that man would have on my life.
John’s achievements, his partnership with Virginia, his presence at the conference mic stand, and his leadership are legendary. I am left flooded with memories, from his collarless dress shirts and fanny pack to his penchant for ice in his Guinness.
I am privileged to have had him as mentor for the last 25 years. His mentorship is evidenced by the many neuropathologists who populate ADRC neuropathology cores or are leaders in our field who continue his life’s work, including Daniel Skovronsky, Andrew Lieberman, Anthony Yachnis, Mark Forman, Peter Nelson, Subhojit Roy, Sriram Venetti, Pallavi Gopal, Aivi Nguyen, Stefan Prokop, and myself.
I am reminded of his impact on the world by the waves of condolences that have streamed in as news of his passing spread from the U.S. to Europe and then Asia. We are profoundly saddened by his death and will carry on in honor of his legacy.
Arizona Alzheimer's Consortium
Like my colleagues, I mourn the loss of our distinguished colleague and friend. I’m extremely grateful to John and Virginia for the quality and breadth of their neuropathological and related neurodegenerative disease research studies, their pioneering contributions to the study of tau, synuclein, TDP43, and mixed pathologies, and the number of amazing people in our field who have benefitted from their mentorship, training, and support. I predict that those people, and those whom they in turn attract to our field, will be John and Virginia’s most important and lasting legacy.
I have always been struck by John’s passion, his fierce advocacy for the fight against these terrible disorders, and his readiness to speak his mind. It is hard not to smile when thinking about all those ADRC Directors meetings, which never seemed to be complete until John shared his point of view.
My heart goes out to Virginia, our colleagues at Penn who continue to advance AD/ADRD research and care in such thoughtful and impactful ways, and all those who have benefitted from their mentorship and support in one form or another. My heart also goes out to our affected patients and families, who lost such a great champion.
New York University
John’s passing is an incalculable loss to the field of neurodegenerative diseases. He had a piercing intellect and was always a delight to interact with. At many conferences, I remember my conversations with him as being the high point of the whole trip. John’s energy and enthusiasm were boundless and highly infectious. He was always insightful and ready to give his forthright comments and opinions on a wide range of topics. He was also highly collaborative and very generous with his time, providing outstanding mentoring advice. My thoughts (and those of the entire NYU ADRC) go out to Virginia and his family.
University of California-San Diego
I worked with John and Virginia on an epidemiologic study of the Chamorro population on Guam. John was always gracious and brilliant. The Alzheimer's field will indeed miss him.
University of Illinois at Chicago College of Medicine
What sad news. The loss of a collaborator and good friend always comes as a shock. As others have already said, John will be sorely missed.
University of North Carolina at Chapel Hill
John will be missed by so many. He was an outstanding communicator about many complex topics within the field of neurodegeneration research.
John was a key member of the Society for Neuroscience Neurobiology of Disease Workshop committee. I was lucky enough to overlap with him for several years on that committee, where I saw his deep commitment to recruiting and training the next generation of scientists focused on translational neuroscience and pathogenesis of neurodegeneration. I vividly remember him bringing up the discovery of TDP-43 accumulation for discussion at that committee, even before the first papers were published. He was clearly excited about this finding and enthusiastic about what it might mean for the future of the field.
I also remember sitting at lunch/dinner tables with him at meetings over the years. He was often engaging trainees and early career scientist in conversation. He displayed genuine interest in what younger scientists were doing and often helped provide context/framing and/or suggestions for collaboration.
UK Dementia Research Institute@UCL and VIB@KuLeuven
John was already a giant when I entered the field, and it was so encouraging to meet him in person, being a funny, creative, and friendly man open for a good discussion. John was one of the founders of the field of dementia research and has, together with his wife, Virginia Lee, pioneered many important breakthroughs. We will miss him deeply.
University of California, Irvine
I had the pleasure of collaborating with John Trojanowski several years ago, when we worked together to make a mouse model that had Lewy bodies, plaques, and tangles. Given that he was such a giant in the field, I was amazed by how quickly he responded to queries not only from me but also from my graduate student. It was a successful collaboration, and a pleasure to work with him.
I also got to see John regularly at the ADRC Directors meeting. He was so impressive and quick-witted, it was difficult not to be in awe of him. We did have a disagreement once, and I remember seeing him across a concrete barrier. To my amazement, he jumped over it, and came up to me and hugged me and said that he sincerely hoped we would continue to be friends. I’m glad we did, as I have always respected him and his work. John was a giant not only in his personal stature but for the field. His legacy and contributions to the field are staggering.
Brigham and Women's Hospital, Harvard Medical School; Broad Institute of Harvard and MIT; Harvard Stem Cell Institute
Like everyone, I was so saddened by news of the great JQT’s passing. I feel especially fortunate that, just last year, he and Virginia hosted me at their Center’s seminar series. I had the opportunity to recount a story of how, like many others, I was brought into the neurodegeneration fold by John. As an intern in medicine looking for a purpose some 20 years ago, I ventured from my native Australia to attend the Short Courses in Neurology at the Institute of Neurology in Queen Square. In a nearby bookstore, I stumbled upon Clark and Trojanowski’s Neurodegenerative Dementias. Despite an outrageous price tag in pounds sterling, I felt compelled to buy it. I read it on the long plane trip home—and was hooked on neurodegenerative disease research for life.
Thereafter, like anyone in neurodegeneration, I have been heavily influenced and inspired by groundbreaking discovery after discovery from John and Virginia’s labs at Penn. I found myself time and time again returning to his classic and authoritative papers and commentaries to ground the interpretation of our own data in the context of human pathology and disease.
When I was a postdoctoral fellow with the late Susan Lindquist, we began to collaborate, and I always found John so insightful, gracious, and helpful. He provided key brain tissue for some of our early work validating iPSC models for familial synucleinopathy. For our functional genomics studies, he unlocked a treasure trove of specimens in the Pathology Department at Penn. Sadly, Sue and John are both now gone, but those projects thrive now in their memory with other wonderful colleagues at Penn.
Thank you to John for being a guiding light to so many of us in this field. We will miss him.
BGI
It's very sad learning that Prof. John Trojanowski passed away. He was such a warm-hearted mentor for young researchers when I stepped into the AD field many years ago. It's a big loss for the AD field. We are going to miss him deeply.
Virginia, please take care yourself. I am sorry for your loss.
Daping Hospital
I and my colleagues were very sorry to hear of John's passing. I first met John and Virginia in May 2018, when I hosted their visit to Chongqing, where Virginia was born. This was the first time that Virginia returned to Chongqing, where she left when she was 2 years old. During their visit we enjoyed very much the time with them to discuss science and neurodegenerative diseases, and were impressed with John's knowledge and personality. I and my colleagues would like to give our sincere thanks to John for his unique contribution to science and generous help to us.
China National Clinical Research Centre for Neurological Diseases，Beijing Tiantan Hospital, CMU
It was impossible for us to believe that Professor John Q. Trojanowski passed away until we checked the website of the University of Pennsylvania. We thank Alzforum for the space to allow us to express our condolences.
Professor John Trojanowski and Professor Virginia Lee visited us in Beijing on May 21, 2018. Professor Trojanowski gave an insightful lecture on dementia, and showed us their human brain banking operation procedures without reservation. Whenever we asked him about the problems that we encountered during the work, he always responded in a timely manner. John was a good mentor and I am grateful for his support. He will be deeply missed.
Abington Neurological
My deep regrets to his family and all those he touched over his long career.
Barrow Neurological Institute
It was devastating to hear of John’s demise. I first met John around 1980 as a postdoctoral fellow at the Harvard Medical School Beth Israel Hospital in Boston. He was visiting to discuss horseradish peroxidase transport techniques for the study of brain pathways. At this time, John was working in the laboratory of Nick Gonatas and was not yet fully immersed in Alzheimer’s research.
I remember this very tall, slender person entering the room wearing a red velvet suit. We all looked at each other, thinking, “Who comes to discuss research in a red velvet suit?” Well, John did!
After our discussions it was clear to everyone that he was a special talent. Little did we know that, over the next four decades, John, with his background in neuropathology complemented by his wife and research partner, Virginia Lee, with her expertise in molecular biology, would form one of the most productive and influential investigative partnerships in the fields of aging and neurological disease research that included Alzheimer’s disease, Lewy body disorders, and TDP-43 proteinopathy in frontotemporal dementia.
Over the years, we became friends with similar interests in understanding the multifactorial nature of Alzheimer’s disease and the need to build brain banks for clinical molecular pathological studies of the onset of dementia. In the late 1990s, when I was planning to organize a program project grant to study the neurobiology of mild cognitive impairment in the elderly, I immediately contacted John and, without hesitation, he was on board. John and Virginia were major contributors to this NIA-funded program project from 1996 to 2006. John brought great encouragement and intellectual guidance to the program. I am forever grateful for his contributions to the program, which is now entering its 23rd year of funding.
John was a giant in the field of neurologic disease research. His generosity and towering intellect will be missed, but his research legacy will influence scientists for generations to come.
My condolences to Virginia. We will miss him!
NYU School of Medicine
With great sorrow, I offer my condolences to the families of John Q. Trojanowski and Virginia Lee. With John’s death, they and the world lost a very special human being. John was a gifted neuropathologist and scientist, an ardent proponent of human rights, a man with good judgement, high intellect, and a cultivated sense of humor.
John and Virginia Lee created a legacy of discovery in Alzheimer’s, Parkinson’s, and other neurodegenerative diseases. This will continue in Virginia’s capable hands. John developed an extraordinary network of colleagues, collaborators, and students. Those of us in any of those categories, like myself, are today and forever aware of the magnitude of the benefit we received by knowing John Q.
University of Kansas
John Trojanowski was one of those larger-than-life exemplars of a generation of AD researchers. His contributions to the field are obviously enormous and enduring. For as long as I have been attending, his input at the semiannual national ADRC meetings was legendary. Shy he was not. Yet, he always seemed to maintain a great sense of humor. I’ll never forget seeing him joking around at dinners. He will live on in so many ways.
John’s pioneering contributions to the field of neurodegenerative disease research were extraordinary, and his presence in the field, like his presence at meetings, was larger than life. The many comments made by others bring back fond memories of his great smile and boisterous laugh in addition to the appreciation of the remarkable scope, volume, and impact of his science.
I was fortunate to collaborate with John on several projects, and he was always generous with his time, support, insights, and resource sharing. I also joined him in annual reviews of applications for the Rotary Coins for Alzheimer Trust (CART) funding. John led the CART Scientific Review Panel for two decades and provided great input and scientific guidance to the CART Grants Committee in selecting the best research to support each year. Two years ago, John stepped down from this role. In appreciation, CART named a grant in his honor, and I hope this precedent will continue. His love for exciting, potentially high-impact research and his commitment to support the careers of young investigators was contagious.
My condolences to Virginia.
China Association For Alzheimer's Disease
On behalf of China Association for Alzheimer's Disease (CAAD), we sent a condolence message on February 9, 2022, as follows:
Shocked to hear of John's sad news, we are deeply saddened, and we would like to express our deep condolences to his dearest wife, Virginia Lee.
The passing of Professor John Q. Trojanowski is a great loss for our scientific community. John was a great scientist who has made important contributions to the study of neuroscience in the world, and he is the closest friend of Chinese and the China Association for Alzheimer's Disease. Professor John Q. Trojanowski had been to China several times, and the scientific concepts and scientific practices he taught in China have always inspired Chinese scientists to keep moving forward, and the scientific flame he sowed will never be extinguished, forever illuminating our way forward.
John is always with us.
National Council of the China Association for Alzheimer's Disease
retired from IIBR
NeuroImmune
NeuroScios GmbH
University of Geneva Medical School Hospitals
All of us at AD/PD were deeply saddened by the news of Prof. John Trojanowski’s demise. He will be universally remembered for his important contributions to neuroscience, for his inquiring mind, and for the large body of work that he produced on neurodegeneration, not the least together with Prof. Virginia Lee.
We at AD/PD feel particularly honored by his regular participation in our meeting. His excellent, tightly packed, and informative presentations were highly appreciated and very well attended. They always were one of the high points of our international conference. His enlightening and challenging presence will be sorely missed.
Our thoughts are with his family and loved ones. The world of AD research lost one of its most prominent scientists.
—Gabriel Gold co-authored this comment.
IRCBC, Chinese Academy of Sciences
I am grateful that I had the chance to be trained by and work with John and Virginia at the Center for Neurodegenerative Disease Research at UPenn during 2013–2019. I think I was John and Virginia’s first of several postdocs with their Ph.D. obtained from China. I knew little about neurodegenerative diseases when I came to CNDR, and John taught me a lot about such mysterious diseases and their neuropathology, raising my strong interests in neuropathology.
I was trained as a neurobiologist, but John provided me the unique opportunity to do brain biopsy, which I could hardly get trained in elsewhere. I used to be only interested in basic research studies, and it was John who encouraged me to interact with clinicians and know what are the really important scientific questions to study, which helped me a lot to do my research from unique points.
In recent years, John kept on encouraging us to think about the pathological comorbidity in neurodegenerative diseases. Alzheimer’s disease is a typical example for such comorbidity in that both Aβ and tau pathogenesis are presented in the disease course. The interactions between two such pathological hallmarks are mysterious, and the consequences of their interaction to AD are largely unclear. It is proposed that Aβ promotes tau-composed neurofibrillary tangle (NFT) formation in AD brains. However, those data were generated from animal models developed by overexpressing mutant tau gene, while overexpression and mutation of tau has never been demonstrated in AD.
At the beginning, we aimed to revisit this Aβ hypothesis in a new system without tau overexpression or mutation. From 2014, along with a former postdoc, Dr. Jing Guo (now at Denali Therapeutics), we first developed a method to extract pathological tau from AD brains in large amounts and with decent purity. Using these human brain-derived pathological tau as the seeds, we were able to induce the endogenous tau in wild-type mouse brain to form similar pathology as in human AD brains (Guo et al., 2016). Using this new system, we moved forward to examine the relationship between Aβ and tau in AD pathogenesis by inoculating human brain-derived AD tau seeds into Aβ mouse models (5xFAD and APP-KINL-F) with the original aim to see whether Aβ mice showed more NFT formation than WT mice. Unexpectedly, we did not observe much NFTs in the 5xFAD mice with already massive Aβ plaques. Instead, we found lots of pathological tau accumulated around Aβ plaques.
We were puzzled about this observation, and asked John whether he saw such a pathological tau pattern. Insightfully, he pointed out that he saw lots of this pattern in human AD brains, and encouraged us to pursue further. We later called such tau pathology neuritic plaque tau (NP tau), and revealed an important discovery that such NP tau might be the very early AD tau form, and could be later transformed or induce NFT formation in connected but far-away neurons (He et al., 2018).
John commented that this study might shift the paradigm in the study of AD, as it provided a new way to think about the interaction between Aβ and tau in the process of AD pathogenesis. The journey of making such discoveries with John and Virginia was really enjoyable.
John also always pointed out the pathological heterogeneity and diversity in neurodegenerative diseases. Tauopathy is such a case, in that although tau deposits are the common feature for AD and frontotemporal lobar degeneration (FTLD), the patterns are distinct. The mechanisms underlying such diversity are largely unknown. One obstacle is the lack of animal models to recapitulate such diverse tau pathogenesis in experimental systems. Inspired again by John, we took the same strategy as we did from AD brains. We enriched pathological tau seeds from distinct tauopathy brain tissues, and inoculated them respectively in a new mouse line developed by Jerry Schellenberg’s lab that expresses 6 human isoform tau in a similar pattern as do normal human brains; we later called this the 6hTau mouse. By doing so, we recapitulated diverse tau pathogenesis as it happens in tauopathy brains, in terms of isoform composition and cell type specificity. Further studies revealed the basis for such tauopathy diversity is the unique pathological tau conformations in distinct diseases (He et al., 2020), which are nicely confirmed by the recent elegant cryo-EM structure works from Michel Goedert and colleagues (Shi et al., 2021).
John was so influential in my career. Since 2020, I have set up my own research group at the Interdisciplinary Research Center for Biology and Chemistry, Chinese Academy of Sciences, to continue my research on neuropathogenesis in neurodegenerative diseases. I am just practicing and spreading my knowledge, techniques, and systems that I learnt from John for studying such devastating diseases to my colleagues in China. John lives forever in my heart.
References:
Guo JL, Narasimhan S, Changolkar L, He Z, Stieber A, Zhang B, Gathagan RJ, Iba M, McBride JD, Trojanowski JQ, Lee VM. Unique pathological tau conformers from Alzheimer's brains transmit tau pathology in nontransgenic mice. J Exp Med. 2016 Nov 14;213(12):2635-2654. Epub 2016 Oct 17 PubMed.
He Z, Guo JL, McBride JD, Narasimhan S, Kim H, Changolkar L, Zhang B, Gathagan RJ, Yue C, Dengler C, Stieber A, Nitla M, Coulter DA, Abel T, Brunden KR, Trojanowski JQ, Lee VM. Amyloid-β plaques enhance Alzheimer's brain tau-seeded pathologies by facilitating neuritic plaque tau aggregation. Nat Med. 2018 Jan;24(1):29-38. Epub 2017 Dec 4 PubMed.
He Z, McBride JD, Xu H, Changolkar L, Kim SJ, Zhang B, Narasimhan S, Gibbons GS, Guo JL, Kozak M, Schellenberg GD, Trojanowski JQ, Lee VM. Transmission of tauopathy strains is independent of their isoform composition. Nat Commun. 2020 Jan 7;11(1):7. PubMed.
Shi Y, Zhang W, Yang Y, Murzin AG, Falcon B, Kotecha A, van Beers M, Tarutani A, Kametani F, Garringer HJ, Vidal R, Hallinan GI, Lashley T, Saito Y, Murayama S, Yoshida M, Tanaka H, Kakita A, Ikeuchi T, Robinson AC, Mann DM, Kovacs GG, Revesz T, Ghetti B, Hasegawa M, Goedert M, Scheres SH. Structure-based classification of tauopathies. Nature. 2021 Oct;598(7880):359-363. Epub 2021 Sep 29 PubMed.
AbbVie
I am saddened to learn of the passing of John Trojanowski. I share many others’ deep appreciation of John Trojanowski’s admirable dedication to science. At my first AD/PD conference presentation, I remember John and Virginia coming over to our poster, kneeling down to the low level of the poster, asking detailed technical questions and giving suggestions to improve the assay. As a graduate student at the time, I found it inspiring to watch accomplished scientists appreciate the convoluted nature of my experimental science, and see their candidness in challenging data interpretations. My condolences to Virginia and the AD field.
John's tragic passing is heartbreaking. We saw John for the last time on 21 September 2014, at our home, near Ulm, for dinner. The next day, he sent us this link with his thank-you note: https://www.youtube.com/watch?v=fdf12InZ-K8&feature=youtu.be.
The CART Fund
Shock and a deep sense of loss were my first emotions when I learned of John's passing. Dr. Trojanowski was so very instrumental in moving our Rotarian grassroots fund raising organization (The CART Fund) from a $100,000 per year contributor to research to $1,000,000 per year. John, Dr. Allan Levey (Emory University), and Dr. Karl Herrup (University of Hong Kong, now University of Pennsylvania) served as the driving force that attracted primary investigators to us for grants. Our young organization grew up under John, Allan, and Karl's leadership and guidance.
I echo Dr. Levey's stated feelings of admiration. The CART Fund family of more than 5,000 Rotarians sends our condolences to all who loved John.
Global Alzheimer's Platform Foundation
John was a wonderful and talented scientist who challenged all of us in the field to do the best science possible. He, along with Virginia, was very committed to identifying the key pathological events leading to Alzheimer's and other neurodegenerative diseases. Over the years I had many conversations with him about when and how to take the insights from basic research on AD to develop potential new medicines that could be entered into clinical development. His standards of scientific excellence were high and the discussions were always stimulating and insightful.
John also had a great sense of humor that came through often unexpectedly. He once misplaced his registration badge at a scientific meeting and, after "borrowing" mine, took delight in convincing a meeting guard that the picture on the badge was him. I recall very fondly a dinner that my wife and I attended with John and Virginia at the home of Chris Clark (unfortunately also deceased) and his wife, Ann. John, as often, led the discussions covering science, politics, cooking, furniture building, and much more. His passing is a great loss to the field.
Medical University Vienna
Returning from holidays, it was a shock to learn about JQT’s passing. The death of such an eminent scientist is a terrible blow to science in general, but still more to a field like neurodegeneration, where personalities able to separate the wheat from the chaff are needed more than ever.
John’s unbelievable scientific achievements have been appropriately described in this line of comments. As a European, I had the opportunity to meet John only at occasional meetings, such as the 50th anniversary of the Japanese Society of Neuropathology in 2009, where all three of us were invited, see photograph. We shared our age and our fascination for neuropathology while always being aware of other essentials in life.
I have always been impressed by John’s attentive, sharp but warm attitude toward others, whoever they were. It was a pleasure and privilege to talk with him not only on research, but on a vast range of topics, from literature to Japanese cuisine. He was a good man.
Virginia, this certainly is most difficult for you. But you can take pride and consolation from the fact you have been the closest to an extraordinary human being.
Virginia Lee and John Q. Trojanowski, fourth and fifth from left.
Boston University School of Medicine
I was shocked to hear that John died. So sad, such a wonderful person and so immensely important for the field. John was always a hero for me, a great scientist and a great person.
I have so many fond memories of conversations with John. First and foremost, John was the towering giant of neuropathology. Working in collaboration with Virginia, he changed our views of the neuropathology of ALS and Parkinson's disease, and impacted immensely on our understanding of AD. Visiting UPenn, giving seminars to the group was always immensely illuminating, productive, and ever so enjoyable ... albeit, always challenging. I remember bringing slides to John to examine, to get his opinion on what I was seeing, then discussing the implications for neuropathology. John was a deep thinker with a penetrating mind and a vast knowledge of neuropathology.
John had a personal side that I equally enjoyed. I found him to be warm and thoughtful, and always enjoyed hearing stories of his life. For instance, I found John’s background surprising. I think he was born into a military family and was an Army brat, following his family among the bases where they lived. As a young man, I think John toyed with being a ballet dancer but chose science, to everyone’s benefit! Tall, lean, and athletic, one can imagine him gliding across a stage. Instead, he commanded the stage as one of the leading minds of our field.
John will be missed by us all.
Goizueta Institute @ Emory Brain Health
John Trojanowski was an iconic figure in our field. I’ll always remember John for both his passion for science and his dedication. Many others have commented on his scientific impact, which we all know was truly impressive. You don’t have an h index greater than 250 and more than 250,000 citations without doing great science. So instead of reviewing his scientific impact, I am going to simply highlight a few of my personal interactions with John, which of course often means with John and Virginia, as well as remind us all that life is sometimes too short and that we should always be grateful and thank those who have helped our careers in various ways before it is too late.
Though I had collaborated and interacted with both John and Virginia during my years as an M.D./Ph.D. student, I really got to know both of them during my residency in laboratory medicine at Penn. They gave me a home in their lab, which at that time was not a sprawling nice space but an old space in the dark basement of the Maloney building. Thanks to them, I was able to do a little research on the side while I completed my residency. What I remember most from those days was the energy and the passion that both John and Virginia had that was really effusive. It was clear that the science came first and they were incredibly dedicated to the mission of discovery science in the neurodegenerative disease space. Of note, even then (1994-97), they were on the hunt for the protein that comprised the mysterious ubiquitylated inclusions in FTD/ALS. So, a simple lesson here is that persistence pays off!
Once I left Penn, John and Virginia remained advocates and helped me at various points in my career. With John’s passing, I regret that I did not get to thank him again. I have had the good fortune of many good mentors, advocates, collaborators, and colleagues, and John was all four.
On my last visit to Penn, I had brought my son Griffin to look at colleges while I was attending and speaking at the ADSP meeting. One night we had dinner with Virginia, John, Gerry Schellenberg, and others, and a lasting memory of John will be his reaching over Virginia to put his hands around Griffin’s neck in a mock strangle accompanied by an impassioned plea of “You must go and do science!” John’s somewhat over-the-top persuasion clearly stuck, as Griffin is pursing biochemistry and working double-digit hours in a lab as a freshman. So, for me John may have had a generational impact, as well.
I, like many others on this memoriam thread, will miss John’s presence. We will miss his scientific insights, his quirky and provocative rebuttals, his preppy, “modish” professorial style, and his friendship.
The University of Queensland
It is very sad to learn that John has passed away. It was via Michel Goedert (who had initiated a collaboration with Kurt Bürki’s team at Novartis back in 1992) that I got to know both John and Virginia at a stage when I had entered the AD space, coming from a different scientific background. They have been an ongoing source of inspiration for me, and I continue to admire their productivity and how they have been moving the field forward at such a pace.
John will be dearly missed, he will be warmly remembered, and my sincere condolences go to Virginia.
Massachusetts General Hospital
I am very saddened to hear about Dr. John Trojanowski's passing. It is a big loss for the field and science. I still remember John and Virginia visiting a conference in South Korea almost 22 years ago, and I was a junior scientist, driving them to the hotel. John asked me about Korean scientists leading the field and AD research in Korea. He was genuinely curious and excited. That 30 minutes completely changed my career track, abandoning a possibly stable position and moving to tackle central questions of AD. I would like to appreciate him motivating many junior scientists like me. Farewell, John.
University of Pennsylvania
I am beyond lucky to have had John as a colleague and mentor. I am forever grateful for his tremendous help and support of me during the past 20 years.
John and Virginia interviewed me in 2001, when they needed a biostatistician to join the Penn neurodegenerative disease research community to build a biostatistics and database infrastructure. During the interview, John’s passion for neurodegenerative disease research was contagious. Later, I found out that this passion was in his blood. I have so many fond memories about John through project meetings, working on grant submissions during winter holidays, traveling to conferences, parties, Institute of Aging Memory Walks, and meeting my family members. He was always eager to learn new things, including statistics. He was such a kind person. I will miss John dearly.
University of Gothenburg
John welcomed me with open arms into the Alzheimer's fluid biomarker field when I started my research there some 20 years ago. I think I first met John when I was a way-too-junior stand-in for a double-booked Kaj Blennow at an important meeting. I was so impressed by his interest, knowledge, enthusiasm, and kindness. On top of this, I thought he looked so much like Mick Jagger. To me, John will always be the rock star of Alzheimer's research.
NeuroTrauma Sciences Inc.
Such sad news. My deepest sympathy to Virginia and John's family. John was a fantastic and giving collaborator and friend. Working with him made you a better scientist and researcher. Knowing him made you a better person.
University of Melbourne
There’s very little I can add to the comments already posted. John was a good friend to all of us, and had interesting connections with Australia. He and I shared a common track in our formative years, coming into the neurodegeneration field through neuropathology and spending some time at the Mass. General Hospital. It’s too early to evaluate his contributions, as the field of research is now moving so rapidly forward, but if I had to predict, I would think that the discovery of TDP43 by him and his team will become the most significant after the dust settles.
I last heard from him in November when I was complaining to him with my reservations about the nosology of Primary Age-Related Tauopathy (PART). He wrote back: “I agree…and while I am in the PART camp I don’t agree with all things PART and wait for more events to accumulate before I can fully decide where I stand.” I think this encapsulates his fair, balanced, and considerate attitude to our scientific explorations. He was very open-minded.
I have a few anecdotes about John, only one of which I can share publicly at this time. When he and Virginia were visiting Melbourne some 10 or more years ago, he asked to use the University gym one evening. I arranged this. A few hours later, I got a call from the University security services saying that they had a problem with an American who had taken over one of the exercise bikes and wouldn’t get off it. They threatened to call the police, but I explained to them who he was, and that it would be in everyone’s interest not to escalate this into an International diplomatic issue. After a bit more negotiation, everyone relaxed when John realized what was going on. I think it was an excellent example of John’s single minded determinist approach to life.
Our deepest sympathies to Virginia, hoping she will have the strength to continue their life’s work. Vale, John.
ADvantage
With deep shock I learned about the premature passing of John Trojanowski, M.D., Ph.D., a pillar in the research on neurodegenerative diseases. I first met John in 1983 at the Society for Neuroscience conference in Boston. At that time, only 8,610 scientists participated in the SfN meeting and John stood out among the audience by getting up and asking many great questions. I remember clearly where he sat in the conference hall because he made such a strong impression on me.
I am confident that others also thought that a new star was born. Since then, he flourished and became an important figure and contributor to the neuropathology of brain diseases. Together with his wife, Virginia Lee, Ph.D., the pair conducted an extensive research program at UPenn and their contributions are immeasurable.
John was the founding director of the NIA-funded Alzheimer Disease Center at UPenn, and I had the honor of serving on an NIA site visit for their program. Then and always, John and Virginia complemented each other so perfectly in their areas of expertise and they were both treated as royalty at all conferences.
RIP, John. You will be dearly missed. I just can’t believe I won’t see you again at the next conference.
Alz Association
The Alzheimer’s Association celebrates the career, character, and contributions of John Trojanowski, M.D., Ph.D. A pioneer and visionary in the field of neurodegeneration, Trojanowski’s monumental career included ground-breaking discoveries, such as uncovering the formation and composition of tau tangles and highlighting their importance across Alzheimer’s and other neurodegenerative diseases.
In 1998, Trojanowski and his wife and research partner Virginia M.-Y. Lee, Ph.D received the Alzheimer's Association’s $1 million Pioneer Award for their project, Alpha-Synuclein, NAC and the Diagnosis of Alzheimer's Disease. Trojanowski received the Khalid Iqbal Lifetime Achievement Award in Alzheimer’s Research at the Alzheimer’s Association International Conference 2018.
Co-founder of ADx NeuroSciences and founder of Key4AD
Biomarkable bvba
Our sincere condolences go to Virginia and her family members. John's research on biomarker integration for individual patient management will be missed a lot. We were privileged to know John for his friendship, and we hope we can carry on part of John and Virginia's legacy of sharing research and friendships into the next generation.
We (Eugeen Vanmechelen and his team) had the pleasure to be invited by John and Virginia in the early days of our biomarker research, in the late '90s. The aim of our visit was to develop highly specific phosphorylated tau assays in CSF. These efforts lead to the development of INNOTEST and INNO-BIA assays (De Meyer et al., 2010) that have been used in many research studies and were the foundation of the multiparameter assay concept used in ADNI (Shaw et al., 2009). Our collaboration continues to today on new biomarker candidates (Goossens et al., 2015; Schmitz et al., 2019).
I personally (Hugo Vanderstichele) remember a meeting with John at a congress around a very small table in a conference center cafeteria during the early days of ADNI. I introduced at that time the concept of multiplex testing of proteins using the xMap (Luminex) technology, developed by us at Innogenetics, now Fujirebio. John was so kind to accept the offer to use the INNO-BIA AlzBio3 for testing ADNI samples. This gave a real boost to my career in the field of neurodegeneration. Together with Les, both inspired me every day to make better products for the field. I will always be grateful for that entry point to the US-ADNI.
References:
De Meyer G, Shapiro F, Vanderstichele H, Vanmechelen E, Engelborghs S, De Deyn PP, Coart E, Hansson O, Minthon L, Zetterberg H, Blennow K, Shaw L, Trojanowski JQ, Alzheimer's Disease Neuroimaging Initiative. Diagnosis-independent Alzheimer disease biomarker signature in cognitively normal elderly people. Arch Neurol. 2010 Aug;67(8):949-56. PubMed.
Shaw LM, Vanderstichele H, Knapik-Czajka M, Clark CM, Aisen PS, Petersen RC, Blennow K, Soares H, Simon A, Lewczuk P, Dean R, Siemers E, Potter W, Lee VM, Trojanowski JQ, Alzheimer's Disease Neuroimaging Initiative. Cerebrospinal fluid biomarker signature in Alzheimer's disease neuroimaging initiative subjects. Ann Neurol. 2009 Apr;65(4):403-13. PubMed.
Goossens J, Vanmechelen E, Trojanowski JQ, Lee VM, Van Broeckhoven C, van der Zee J, Engelborghs S. TDP-43 as a possible biomarker for frontotemporal lobar degeneration: a systematic review of existing antibodies. Acta Neuropathol Commun. 2015 Apr 1;3:15. PubMed.
Schmitz M, Villar-Piqué A, Llorens F, Gmitterová K, Hermann P, Varges D, Zafar S, Lingor P, Vanderstichele H, Demeyer L, Stoops E, Trojanowski JQ, Lee VM, Zerr I. Cerebrospinal Fluid Total and Phosphorylated α-Synuclein in Patients with Creutzfeldt-Jakob Disease and Synucleinopathy. Mol Neurobiol. 2018 Aug 22; PubMed.
University of California, San Diego
I have greatly valued John’s enormous contributions in the field of molecular neuropathology relevant to Alzheimer’s and had the privilege of collaborating with him on several projects over the years. One of these areas was ALS-PDC of Guam, where John analyzed brain tissue that we collected from Chamorros with Parkinson-Dementia Complex and other dementias. John’s usual articulate, forceful, and vibrant personality, infused with input and ideas from Virginia, his scientific and life partner, greatly helped us to conceptualize how we might frame pathological and biochemical changes in the brain in ALS-PDC in the context of Alzheimer’s disease, other tauopathies, and ALS. And, with his background—as he told us—of growing up as a “military brat” and living in many different places, he gladly made the very long trip to Guam to give a presentation as part of the educational outreach that our project conducted to promote research to the community.
John made a pitch for the importance of brain donation, and I remember his presentation of protein misfolding for a lay audience—he dramatically held up a piece of paper, then crumpled it up and dropped it on the floor, saying that after the paper was badly folded like this, it was no longer useful, and that something similar was happening in the brain. John’s energy, breadth of knowledge, enthusiasm, and methodological rigor coupled with his ability to collaborate with and organize multidisciplinary research groups, have enriched the field and left a spectacular scientific legacy.
Massachusetts General Hospital
So much has been said about the monumental contributions to AD and FTLD research by John—still, we would need thousands more commentaries to cover it all.
I remember John as a warm, incredibly compassionate and fun human being. I would have to say that among the times I look back at over the past decades in this field, those that were the most enjoyable and fun were with John and Virginia.
Virginia, please know you have my deepest condolences.
May John's pioneering scientific achievements, amazing spirit, and, especially, his love of life and friends, live on in all all of us!
We will all miss you, John. I personally will miss our long-time friendship, laughter, thoughtfulness, and hope the Institute of Aging will continue to prosper. My very best regards and deepest empathy for Virginia. He will always be a rock star.
Free University of Brussels, Faculty of Medicine
John was a giant in the field of neurodegenerative diseases. His numerous scientific contributions, made with his wife, Virginia, over the decades, speak for themselves.
John had a special elegance and courtesy with colleagues, making him such an enjoyable person and scientist to engage. John and Virginia had a unique combined expertise, ranging from biochemistry to neuropathology, that resulted in such a successful scientific career. At the time when tau research was somehow relatively neglected, it was a a pleasure (and a comfort) to have John keeping working in this area.
John and Virginia were keen to help funding organizations with their expertise. On several occasions when we met, I was reminded how kindly and professionally they participated in review boards in Paris and in other European countries soon after the arrived, despite being tired by jet lag.
We will greatly miss him. My condolences go to Virginia, too.
R&R Perez LLC
What a great loss ... it is hard to imagine attending neurodegeneration conferences without hearing John's wonderful voice and hardy laugh as he thoughtfully challenged everyone to go deeper.
In the early 2000's, I was thrilled to be invited to present my research at U Penn and meet with John and Virginia and their many talented lab members. Over the years I have continued to be grateful for their support and ongoing contributions to the field.
Rest in peace John, and thanks always for your unique way of thinking about nature and medicine.
Harvard Medical School
John was a true friend and a great scientist. He was unique in our field, not only because of the breadth of his intellect and contributions, but because he brought a very classy style to his interactions and science. It is something from an era long gone that John really embodied. In a way, he elevated the science to a higher plane. It was also fun when we got together and reminisced, since we moved through many of the same institutions during our training. I will miss him.
Florida State University
I met John and Virginia when I first joined U Penn in 1986. We worked together on a Program Project, the brain bank, and we collaborated on research for over 10 years. I spent many hours in the autopsy suite of the old hospital, often at night, with John. He was a mentor, even though we were not all that many years apart, an intellectual sparring partner, and he cared about his friendships. He drove, occasionally, a beautiful old BMW, when not on his bike. I could never understand how he managed the Philadelphia streets going back and forth to U Penn. I truly thought he would go on forever.
New York University School of Medicine/Nathan Kline Institute
My friendship with John and Virginia dates back to John’s years at MGH and even earlier, to Virginia’s in the HMS neuroscience dept. Our kindred scientific interests and countless gatherings at conferences and site visits made “growing up” with John and Virginia in those early days of AD research feel more like a sibling experience than just a collegial one. John’s neuropathology knowledge and intuition, complementing Virginia’s expertise in cell biology, seemed from the start to be the right approach to this complex disease, and it ultimately proved to be a winning formula behind their incredibly meaningful impact on our field.
Shining through John’s science over the years are his ecumenical perspective on AD pathogenesis and appreciation of the powerful insights to be gained from seeking mechanistic commonalities across different neurodegenerative disorders. His steadfast conviction and impassioned defense of these positions have been a crucial conceptual rudder, keeping the field on course and giving crucial support to those paving new paths toward understanding AD.
Words are insufficient to convey my deepest condolences to Virginia.
Ottawa Hospital Research Institute
The news of Dr. John Q. Trojanowski’s untimely death and the many tributes to his life have travelled around the globe. As his colleagues, our collective condolences go to his and Virginia’s family, their circle of friends, and to his institution. It is difficult to envision a future meeting in the field of neurodegeneration without John's towering figure and deep voice, without his roaring laughter, and without the probing questions he invariably posed, as informed by his keen curiosity and delivered with unique cadence and eloquence.
To my mind, three encounters personify part of who John was. In 1989, I was introduced to John by my then-supervisor, Dennis Selkoe, at a neuropathology meeting in Baltimore. Upon hearing of my upbringing in Vienna, John fluently addressed me in German and told me of his post-collegiate time spent at the University of Vienna, where, as he pointed out, he dabbled for a while in theater and drama before turning to medicine and science. I was a bit awestruck and said to Dennis, “This man’s facial expressions and demeanor remind me so much of Mick Jagger.” John's dark professorial spectacles further accentuated his commanding presence.
A second encounter occurred in Dubai, UAE, in 2008, at a conference Omar El-Agnaf had organized, and where Virginia first presented some of their joint work on α-synuclein fibril propagation. After a late and lively dinner with Virginia, John, and Omar at a restaurant near the world’s largest tower, Burj Khalifa, I spotted John and Virginia both working out vigorously in the gym of our hotel the following day, well before the meeting’s first morning session. After completing my own 30-minute routine, John and Virginia were still at it on the treadmill and elliptical, respectively. I was about to leave, when John roared, “Michael, there is only one way to avoid the neurodegenerative disorders we study in the elderly, and that is exercise … and Virginia and I are committed to doing everything to stay fit!” Ever since then, I watched John as he took podium after podium with a youthful spring in his step up to the lectern. It is doubly tragic that his death followed from complications of a fall.
A third defining moment for me was the 2005 SfN meeting where we discussed both the unexpected finding of parkin’s significant insolubility in adult human brain that their team had published a few months earlier (Pawlyk et al., 2003), and work that Matthew LaVoie and I were pursuing on parkin in dopamine cells (LaVoie et al., 2005). John became philosophical: “Throughout my career, I've never seen a protein transition from soluble to insoluble in healthy human brain but not aged animal brain. I don’t know what it means for its function; someone else has to figure this out and explain it to me. I am pretty confident we got this [biochemical behavior] right because of the strength of the antibodies we generated.” His honest, humble admission of having no answer to a puzzling problem further motivated me in my own parkin research. In the spring of 2021, following publication of our paper suggesting an explanation for the phenomenon of parkin’s physiological transition (Tokarew et al., 2021), John, Virginia, and I exchanged e-mails that ended with his message “… and we are fine as well.” Sadly, due to pandemic restrictions to in-person international meetings, our follow-up discussions never took place.
I am eagerly awaiting how journals, John’s institution, our field, and his country will honor this man, who dedicated his career to the understanding of neurodegeneration. John, we will miss your presence, your youthful energy and your intellectual prowess. Rest in peace!
References:
Pawlyk AC, Giasson BI, Sampathu DM, Perez FA, Lim KL, Dawson VL, Dawson TM, Palmiter RD, Trojanowski JQ, Lee VM. Novel monoclonal antibodies demonstrate biochemical variation of brain parkin with age. J Biol Chem. 2003 Nov 28;278(48):48120-8. PubMed.
LaVoie MJ, Ostaszewski BL, Weihofen A, Schlossmacher MG, Selkoe DJ. Dopamine covalently modifies and functionally inactivates parkin. Nat Med. 2005 Nov;11(11):1214-21. PubMed.
Tokarew JM, El-Kodsi DN, Lengacher NA, Fehr TK, Nguyen AP, Shutinoski B, O'Nuallain B, Jin M, Khan JM, Ng AC, Li J, Jiang Q, Zhang M, Wang L, Sengupta R, Barber KR, Tran A, Im DS, Callaghan S, Park DS, Zandee S, Dong X, Scherzer CR, Prat A, Tsai EC, Takanashi M, Hattori N, Chan JA, Zecca L, West AB, Holmgren A, Puente L, Shaw GS, Toth G, Woulfe JM, Taylor P, Tomlinson JJ, Schlossmacher MG. Age-associated insolubility of parkin in human midbrain is linked to redox balance and sequestration of reactive dopamine metabolites. Acta Neuropathol. 2021 May;141(5):725-754. Epub 2021 Mar 10 PubMed.
ClinicalTrials Planning LLC
The trajectory of ALS neuropathology, from the Bunina body to ubiquitin inclusions and finally the TDP-43 inclusions, anatomically identified a crucial pathogenic target that has opened up a pathway toward future treatment. Correlating the topographical pathological findings with clinical milestones was the common goal that brought me to John at times, seeking insights and directions. Discussing experiences at the Massachusetts General Hospital and in Vienna, Austria, in the late 1960s was a common source of shared nostalgia.
University of Texas at San Antonio
A Giant Among Us
It was not John’s 6-foot, 4-inch lean frame that filled the space but the breadth of his accomplishment, generosity of service, and friendship. John’s (often with Virginia) scientific firsts are recounted by others. What I mourn is the loss of his inspiration, whether it be as his colleague or competitor, as there are none better to inspire the ultimate in perfection. When others were content with one or two lines of evidence to support an argument, John displayed what seemed to be dozens—proof he must have never slept. Yet he did all with a relaxed tone of joy admired by all. For an obituary in JAD, see https://content.iospress.com/articles/journal-of-alzheimers-disease/jad2....
EPFL/ND BioSciences
During the past weeks, scientists, students, organizations, and patient groups from all over the world have been mourning the loss of Prof. John Q. Trojanowski—legend, icon, larger-than-life figure in the field of neurodegenerative diseases. He is also remembered as a brilliant, classy man, a warm-hearted and caring mentor, and a kind friend. While reading the above tributes and memorable moments from former students, trainees, and colleagues, I struggled with the question of how do you mourn the loss of someone who is still giving, teaching, inspiring, and shaping the lives and work of many people in so many ways?
I struggled to find the best way to honor John and describe his work and achievements in ways that will do him justice. After reading some of his interviews and hearing some of the beautiful analogies he used to communicate complex concepts in NDDs and his views on different topics and controversies, I realized no one is more qualified to tell the world about John than John, with only one exception: his life and work partner, Dr. Virginia Lee.
I published in a separate place my humble attempt to use John’s, and occasionally Virginia’s, words to provide a glimpse of his vibrant personality, research philosophy, and some of the guiding principles and hypotheses that defined his work and contributions to the field of NDDs. Read the article here: https://www.nature.com/articles/s41531-022-00310-1.
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