Neuropathologist Charles Duyckaerts Passes Away at Age 70

After several years of battling illness, Charles Duyckaerts, a stalwart of dementia neuropathology, passed away August 6. He was 70. Perhaps best known for his work on the spread of neurofibrillary tangles, Duyckaerts also studied amyloid plaques, Lewy bodies, TDP-43 aggregates, and other neuropathological aggregates.

Charles Duyckaerts by Benoit Delatour.

In a career that spanned five decades, much of it at the Hôpital de la Pitié-Salpêtrière, Paris, Duyckaerts was one of the first to connect neurofibrillary tangles to cognitive decline (Duyckaerts et al., 1997). Using fine-grained neuropathological analyses, he led efforts to find connections between tangles and amyloid deposits, the other major neuropathological hallmark of AD (Duyckaerts, 2004). Along the way, he found that plaques contained much cholesterol, and that the ApoE4 allele tended to come with greater plaque load, soon after it had been genetically linked to the disease (Panchal et al., 2010; Berr et al., 1994). 

Interested in prion-like propagation of pathological proteins, Duyckaerts studied and compared the spread of tau in AD and in primary tauopathies (Hauw et al., 1990). 

“Charles’s intellectual rigor, encyclopedic knowledge, and curiosity enabled him to break through barriers of traditional neuropathology, to explore new microscopies, the most advanced analytical techniques, modeling, and mathematical morphology tools,” noted Marie-Claude Potier, Benoit Delatour, and Stephane Haik, colleagues from Pitié-Salpêtrière.

Duyckaerts adopted CLARITY, a whole-brain-clearing technique for microscopy (Apr 2013 news), to study human plaques and tangles in situ (Ando et al., 2014). He led one of only a few groups to realize that Aβ and tau might be transmitted iatrogenically from person to person via batches of human-tissue-derived growth hormone or dural grafts (Duyckaerts et al., 2018; Herve et al., 2018).

Not one to shy away from controversy, Duyckaerts argued that primary age-related tauopathy was nothing more than an early form of AD (Duyckaerts et al., 2015). “One always came away transformed by the lively scientific discussions or histological slide sessions he led,” wrote Potier and colleagues.

In 2018, Duyckaerts gave a keynote at the Human Amyloid Imaging conference in Miami Beach, Florida, that is still playable on HAI's website. (Click 2018 tab.)

Did you know Charles?  If you would like to commemorate his life and career by sharing a story, anecdote, or memory, please use the comment box below.—Tom Fagan

Comments

  1. Charles’ intellectual rigor, encyclopedic knowledge, and curiosity enabled him to break through barriers of traditional neuropathology, to explore new microscopies, the most advanced analytical techniques, modeling, and mathematical morphology tools. He was impressed by hard science. In the research team, one always came back transformed by the lively scientific discussions and histological slide sessions he led. He did not trust beliefs and loved new hypothesis, new questions to be answered ASAP. His outstanding teaching and communication skills were much appreciated and he selflessly devoted his time to researchers and students. He was a model of humanity in the scientific world. We, members of the research team Charles belonged to, will deeply miss him. As teacher, mentor, colleague, and friend, he gave us so much. He will remain engraved in our memories.

    View all comments by Marie-Claude Potier View all comments by Benoît Delatour View all comments by Stéphane Haïk

  2. Charles Duyckaerts was a highly accomplished neuropathologist. He made important contributions to our understanding of many neurodegenerative diseases, but we limit our comments to assembled tau and Alzheimer’s disease (AD).

    Experimental evidence for the prion-like spreading of assembled tau left open the question if prion-like spreading also occurs during the development of AD. Reaching Braak stages V and VI requires going through Braak stages I-IV first. Consequently, Duyckaerts et al. (2015) proposed that primary age-related tauopathy (PART) is part of AD. This is supported by the identical cryo-EM structures of tau filaments from AD and PART (Shi et al., 2021). 

    The paper by Duyckaerts et al. of 1997, at a time when the concept of prion-like propagation of non-prion protein assemblies was in its infancy, is one of the strongest pieces of evidence in favor of the prion-like spreading of tau assemblies in human brain. Duyckaerts and colleagues reported the absence of tau pathology in a frontal cortical region that had been anatomically disconnected from the limbic region as a result of neurosurgery decades before the patient developed AD. This was the case, despite extensive tau pathology in adjacent brain areas, as well as in limbic and isocortical regions.

    Charles was a kind and humble person, whose interests went much beyond neuroscience. He will be sorely missed.

    References:

    Duyckaerts C, Uchihara T, Seilhean D, He Y, Hauw JJ. Dissociation of Alzheimer type pathology in a disconnected piece of cortex. Acta Neuropathol. 1997 May;93(5):501-7. PubMed.

    Duyckaerts C, Braak H, Brion JP, Buée L, Del Tredici K, Goedert M, Halliday G, Neumann M, Spillantini MG, Tolnay M, Uchihara T. PART is part of Alzheimer disease. Acta Neuropathol. 2015 May;129(5):749-56. Epub 2015 Jan 28 PubMed.

    Shi Y, Murzin AG, Falcon B, Epstein A, Machin J, Tempest P, Newell KL, Vidal R, Garringer HJ, Sahara N, Higuchi M, Ghetti B, Jang MK, Scheres SH, Goedert M. Cryo-EM structures of tau filaments from Alzheimer's disease with PET ligand APN-1607. Acta Neuropathol. 2021 May;141(5):697-708. Epub 2021 Mar 16 PubMed. Correction.

    View all comments by Michel Goedert View all comments by Maria Grazia Spillantini

  3. Charles Duyckaerts was active in the field of Alzheimer’s research, although his expertise was not limited to this disease, and in many aspects he was a pioneer in this field for almost 40 years. I was happy to have Charles as a friend, and a collaborator on many occasions.

    Charles was of Belgian origin, born in Liège, but spent most of his career in the Pitiè-Salpétrière hospital in Paris, notably as head of the Laboratoire de Neuropathologie Raymond Escourolle. He retained much affection for the relatively small country he came from, and, on many occasions we laughed when colleagues called us part of a “Belgian team.”

    Charles was polite and kind, with a natural elegance (some people would say a neuropathologist's elegance ...). His ever-smiling courtesy made him a pleasant person to talk to, and I benefitted from that so often. I was lucky to have him as a jury member of my Ph.D. thesis.

    We met with my late mentor, the neuropathologist Prof. J. Flament-Durand, and started to collaborate during an EURAGE meeting in Newcastle upon Tyne, U.K., organized in 1985 by J. Edwardson and B. Tomlinson, for whose seminal clinicopathological studies in AD Charles had great admiration. EURAGE was focused on dementia and aging research in Europe. These meetings were significant in gathering several European laboratories interested in this still relatively “emerging” field.

    Charles was instrumental in organizing comparative studies of neuropathological criteria for Alzheimer's from different laboratories, including ours (Duyckaerts et al., 1990). In his laboratory, scientists used their clinically and neuropathologically well-characterized Charles Foix cohort to make clinicopathological correlations (Duyckaerts et al., 1985). Charles maintained a deep interest in those neuropathological criteria and participated with colleagues in many studies proposing neuropathological guidelines (and correlative studies with cognitive status) (Montine et al., 2012). 

    I was lucky to provide Charles with our recently developed anti-PHF and anti-tau antibodies, which he used for the first time in studies assessing their value in clinicopathological quantitative correlative studies of AD (Delaère et al., 1989; Duyckaerts et al., 1987). 

    Charles was keen to investigate and adopt new research methodologies. He was at ease with stereological analyses and developed dedicated software programs aimed at mathematical analysis of neurons, NFT and senile plaque densities and distribution (Duyckaerts et al., 1994). His team was the first to apply tissue-clarification methods to the study of AD pathology in postmortem human tissue (Ando et al., 2018; Ando et al., 2014).

    He was co-director (with Stephane Haïk and Marie-Claude Potier) of the Alzheimer’s and prions research team in ICM in Paris for several years, pointing to his interest in studying the relationship between these diseases. Charles, like many researchers in this field, was intrigued by the potential prion-like transmissibility of protein seeds in neurodegenerative diseases. He contributed many recent papers to this topic, and we enjoyed collaborating with him in a study in iCJD (Duyckaerts et al., 2018). 

    Charles got a Henry Wisniewski Lifetime Achievement Award in in 2006. He was at the foundation of the brain bank Neuro-CEB in France. With its associated neuropathologist network, Neuro-CEB has contributed to many fundamental studies by providing scientists with precious and rigorously characterized brain tissue samples.

    Charles was a passionate scientist, always ready to discuss the latest findings, and potential bias, of most recent data shedding light on the longstanding problem of the relationship between senile plaques and neurofibrillary tangles. He was always questioning data in a way that often led me to carefully reconsider strong assumptions about the respective roles of plaques and tangles (Duyckaerts et al., 2015). 

    Charles was convinced of the importance of neuropathology for fundamental research and for understanding the complexity of dementing diseases, and he advocated for this at all levels of political decisions for scientific research. I have often been impressed by the cleverness of his work, sometimes designed almost as experimental studies assessing the role of connectivity in propagation using neuropathological material (Duyckaerts et al., 1997; Thierry et al., 2020) or animal models (Delatour et al., 2004). 

    Charles had many national and international collaborators not quoted in this personal tribute. He was modest about his scientific contributions, although they are numerous. He was ranked as a highly quoted researcher in the Clarivate Web of Science.

    Charles spoke enthusiastically about science whenever you called him. I will miss him, his rigor and vast knowledge of the field, and his pleasant personality. My deepest sympathy goes to his family, his wife, Patricia, and his three children.

    References:

    Ando K, Laborde Q, Brion JP, Duyckaerts C. 3D imaging in the postmortem human brain with CLARITY and CUBIC. Handb Clin Neurol. 2018;150:303-317. PubMed.

    Ando K, Laborde Q, Lazar A, Godefroy D, Youssef I, Amar M, Pooler A, Potier MC, Delatour B, Duyckaerts C. Inside Alzheimer brain with CLARITY: senile plaques, neurofibrillary tangles and axons in 3-D. Acta Neuropathol. 2014 Sep;128(3):457-9. Epub 2014 Jul 29 PubMed.

    Delaère P, Duyckaerts C, Brion JP, Poulain V, Hauw JJ. Tau, paired helical filaments and amyloid in the neocortex: a morphometric study of 15 cases with graded intellectual status in aging and senile dementia of Alzheimer type. Acta Neuropathol. 1989;77(6):645-53. PubMed.

    Delatour B, Blanchard V, Pradier L, Duyckaerts C. Alzheimer pathology disorganizes cortico-cortical circuitry: direct evidence from a transgenic animal model. Neurobiol Dis. 2004 Jun;16(1):41-7. PubMed.

    Duyckaerts C, Braak H, Brion JP, Buée L, Del Tredici K, Goedert M, Halliday G, Neumann M, Spillantini MG, Tolnay M, Uchihara T. PART is part of Alzheimer disease. Acta Neuropathol. 2015 May;129(5):749-56. Epub 2015 Jan 28 PubMed.

    Duyckaerts C, Brion JP, Hauw JJ, Flament-Durand J. Quantitative assessment of the density of neurofibrillary tangles and senile plaques in senile dementia of the Alzheimer type. Comparison of immunocytochemistry with a specific antibody and Bodian's protargol method. Acta Neuropathol. 1987;73(2):167-70. PubMed.

    Duyckaerts C, Delaère P, Hauw JJ, Abbamondi-Pinto AL, Sorbi S, Allen I, Brion JP, Flament-Durand J, Duchen L, Kauss J. Rating of the lesions in senile dementia of the Alzheimer type: concordance between laboratories. A European multicenter study under the auspices of EURAGE. J Neurol Sci. 1990 Jul;97(2-3):295-323. PubMed.

    Duyckaerts C, Godefroy G, Hauw JJ. Evaluation of neuronal numerical density by Dirichlet tessellation. J Neurosci Methods. 1994 Jan;51(1):47-69. PubMed.

    Duyckaerts C, Hauw JJ, Piette F, Rainsard C, Poulain V, Berthaux P, Escourolle R. Cortical atrophy in senile dementia of the Alzheimer type is mainly due to a decrease in cortical length. Acta Neuropathol. 1985;66(1):72-4. PubMed.

    Duyckaerts C, Sazdovitch V, Ando K, Seilhean D, Privat N, Yilmaz Z, Peckeu L, Amar E, Comoy E, Maceski A, Lehmann S, Brion JP, Brandel JP, Haïk S. Neuropathology of iatrogenic Creutzfeldt-Jakob disease and immunoassay of French cadaver-sourced growth hormone batches suggest possible transmission of tauopathy and long incubation periods for the transmission of Abeta pathology. Acta Neuropathol. 2018 Feb;135(2):201-212. Epub 2017 Nov 22 PubMed.

    Duyckaerts C, Uchihara T, Seilhean D, He Y, Hauw JJ. Dissociation of Alzheimer type pathology in a disconnected piece of cortex. Acta Neuropathol. 1997 May;93(5):501-7. PubMed.

    Montine TJ, Phelps CH, Beach TG, Bigio EH, Cairns NJ, Dickson DW, Duyckaerts C, Frosch MP, Masliah E, Mirra SS, Nelson PT, Schneider JA, Thal DR, Trojanowski JQ, Vinters HV, Hyman BT, . National Institute on Aging-Alzheimer's Association guidelines for the neuropathologic assessment of Alzheimer's disease: a practical approach. Acta Neuropathol. 2012 Jan;123(1):1-11. PubMed.

    Thierry M, Boluda S, Delatour B, Marty S, Seilhean D, Brainbank Neuro-CEB Neuropathology Network, Potier MC, Duyckaerts C. Human subiculo-fornico-mamillary system in Alzheimer's disease: Tau seeding by the pillar of the fornix. Acta Neuropathol. 2020 Mar;139(3):443-461. Epub 2019 Dec 10 PubMed.

    View all comments by Jean-Pierre Brion

  4. Charles combined two great characteristics: dur as the scientist-pur-sang that he was, and trés aimable in all other aspects!

    I had the opportunity and privilege to invite and welcome Charles comme expert en neuropathologie on one of our one-day AD-symposia and comme membre externe du jury of my one-but-last Ph.D. student (No. 16 in 2013).

    I also applauded him on being the first to use the term "spreading" vàv tau pathology—already back in 1990! (Hauww et al., 1990)—to which he modestly replied: "But to reduce our merit to its real proportions ... real neuropathologists ... believed that tau pathology progressed through connection."

    We will miss him!

    References:

    Hauw JJ, Verny M, Delaère P, Cervera P, He Y, Duyckaerts C. Constant neurofibrillary changes in the neocortex in progressive supranuclear palsy. Basic differences with Alzheimer's disease and aging. Neurosci Lett. 1990 Nov 13;119(2):182-6. PubMed.

    View all comments by Fred Van Leuven
    • User Profile Image Nicolas Villain
      Sorbonne University - APHP - Pitié-Salpêtrière Hospital
    • Posted:

    When I first met Charles, I was a young Ph.D. student attending a local conference in Caen, France, in 2007. I was very impressed by his vision and rigor: He was the first pathologist I met and read who gave me answers to neuroimaging and network issues I was facing during my Ph.D. I then asked him if he would agree to be the rapporteur for my Ph.D. defense and was honored to have him and his brilliant mind on my jury, although the central methodology of my thesis was far from his field of competence. Charles' strength has always been to go beyond classical neuropathology to encompass and solve scientific questions.

    When I finally trained in Paris as a neurologist, I was able meet him again and be part of his former research group, now led by Marie-Claude Potier and Stéphane Haïk. Again, his encyclopedic knowledge and rigor impressed me. While fighting his illness, he remained involved in science with modesty and gave much of his time to relevant feedback on ongoing research projects.

    As mentioned in the obituary, Charles contributed much to the field, keeping a sharp eye on a vast domain. He enabled those he worked with to become better people and better scientists. We will miss him deeply.

    View all comments by Nicolas Villain

  6. A great scientist and inspiring person. He will be missed.

    View all comments by Susana Boluda

  7. Having known Charles for a long time, I remember how he was always enthusiastic, open to new hypotheses and to answering new questions, and ready to collaborate. It was a great pleasure to discuss science with him in all simplicity and friendship, which enabled the sharing of his encyclopedia knowledge. We will deeply miss Charles and he will always be in our memories.

    View all comments by Bernadette Allinquant

  8. It is very sad to receive the message that Professor Charles Duyckaerts has passed away. His research period as an important, creative, and inspiring neuropathologist covers many decades, and his experimental evidence of prion-like spreading of tau in brain still generates studies to further understand the possible underlying mechanisms in AD.

    I had the pleasure to meet Charles at several conferences, often engaging in lively discussion of the pathological characteristics of different tauopathies and how the introduction of new tau PET tracers could provide further insights in vivo into early disease mechanisms of AD and primary tauopathies. I was happy when Charles accepted the invitation to participate in our Nobel Forum symposium “Alzheimer’s Disease and Other Proteinopathies—Drug Targets” at Stockholm’s Karolinska Institutet in 2017.

    Charles gave, as always, an elegant and inspiring lecture, “Synergy Between Tau and Aβ Pathology,” which generated from the audience many questions and discussions that Charles seemed to enjoy. Dr. Laetitia Lemoine and I have, in collaboration with Charles, an unfinished in vitro autoradiography-binding study on multiple PET tracers in brain tissue sections from a large collection of different tauopathies, whose neuropathology was extensively characterized by Charles.

    The manuscript will now be completed and submitted in appreciation and memory of Charles Duyckaerts.

    View all comments by Agneta Nordberg
    • User Profile Image Kunie Ando
      Free University of Brussels
    • Posted:

    Professor Duyckaerts had a deep and broad knowledge of neuropathology and the molecular mechanisms of neurodegeneration. At the time I was working with him at ICM as a postdoc from 2011 to 2014, he was quite busy as the director of neuropathology laboratory of Raymond Escourolle, co-director of the Alzheimer's and prion team at ICM institute, and director of the NeuroCEB brain bank of postmortem tissues. Charles worked hard every day from Monday to Saturday, starting early in the morning with his neuropathological session at the multi-head microscopes with his colleagues and finishing late on his PC to polish the papers of his postdoc and Ph.D. students. He often worked Sunday to write his papers or correct our manuscripts.

    As anybody who worked with Charles would agree, he was a wonderful model to his colleagues. Despite a heavy workload, he was always so elegant, humble, and happy to help his colleagues, students, and trainees. I need to underline his dedication to the Brain Bank NeuroCEB Neuropathology Network that has significantly contributed to research advancement on various neurodegenerative diseases.

    Charles was also such a warm-hearted, kind, and respectful person. Words cannot express my sorrow. We will miss him so deeply.

    In July 2014, at ICM institute in la Pitié-Salpêtrière hospital, Paris. Prof. Charles Duycakerts (center) and his colleagues.

    In July 2014, Prof. Charles Duyckaerts (right) with his Belgian friends, Professor Jean-Pierre Brion (center) and Professor Jean-Noël Octave (left) in Copenhagen, Denmark.

    View all comments by Kunie Ando

  10. Charles was a respected colleague for more than three decades, as well as a collaborator on international initiatives on the neuropathology of aging and dementia, including two iterations of the neuropathologic criteria for PSP, the most recent of which was completed only months before he died. I fondly remember participating in courses he organized in the south of France, and especially the opportunity to present at the famous Salpêtrière Institute in Paris at his invitation. Charles was not only a great neuropathologist and a scientist, but also a humanist and a valued friend. I will forever remember his personally guided tour of the Louvre and his love of Paris.

    We will miss him, but we celebrate his many contributions to neuropathology.

    References:

    Roemer SF, Grinberg LT, Crary JF, Seeley WW, McKee AC, Kovacs GG, Beach TG, Duyckaerts C, Ferrer IA, Gelpi E, Lee EB, Revesz T, White CL 3rd, Yoshida M, Pereira FL, Whitney K, Ghayal NB, Dickson DW. Rainwater Charitable Foundation criteria for the neuropathologic diagnosis of progressive supranuclear palsy. Acta Neuropathol. 2022 Oct;144(4):603-614. Epub 2022 Aug 10 PubMed.

    View all comments by Dennis Dickson
    • User Profile Image Yuichi Riku
      Aichi Medical University, Nagoya University
    • Posted:

    Charles Duyckaerts was an outstanding neuropathologist and educator. I worked with him at the neuropathology laboratory of Raymond Escourolle, Pitié-Salpêtrière, from 2017 to 2019. Charles often told interesting episodes in the face of a single, simple H-E slide. Also, he was a warm man. I remember that he invited me to his house two days before my return to Japan. He made a great dinner, and I said, "You are as good at cooking as well as neuropathology!" He smiled shyly and said, "I am really an amateur. My wife is the teacher of all about cooking."

    I believe Charles’s neuropathology will develop further and help save many patients with neurological disorders.

    View all comments by Yuichi Riku

  12. Charles Duyckaerts' passing away has deeply upset us all. As a young researcher, I worked with Charles for four years in his lab at Escourolle and at the Institut du Cerveau in Paris.

    I greatly appreciated his human qualities. He was honest, humble, a very good pedagogue, expecting us to do our job well, yet giving us full freedom to create. He was totally invested in his work. He had a true sense of ethics in research. I am indebted to him for transmitting his knowledge and values.

    When I joined the Fondation Vaincre Alzheimer, I was honored that he agreed to be the president of our Scientific Advisory Board, then a member of our Scientific Development Committee. I continued to work with him, relying on his great qualities as a scientific reviewer and on his enlightened vision of the world of research. Our foundation supports the brain bank NeuroCEB, and I know how much he was invested in the creation and evolution of this unique organization in France. We are honored to support and develop this biobank.

    He was undeniably my mentor for all these years, and I will miss him deeply.

    View all comments by Maï Panchal

  13. I met Charles more than 30 years ago and thereafter we met frequently, always with great pleasure. As a young researcher, mainly trained in enzymology and cell biology, I have to admit that I considered anatomical pathology a rather static view of biological processes. Charles really opened my eyes by talking about it in such a lively way. And thus, I understood to which extent the in situ observations could unravel biological processes. Indeed, in my laboratory, I am currently approaching several neurodegenerative diseases by combining not only cellular and biological aspects but by trying to complement through the eye of morphologists and anatomists.

    Charles was more than a colleague, with the rare ability of listening to others without being dogmatic. Charles' legacy for science is huge. The scientific community will miss a fantastic scientist. I will miss a good friend.

    View all comments by Frédéric Checler

  14. The news of Charles Duyckaerts' passing came as a shock. I met Charles at the Charité Entrepeneurship summit in Berlin on May 28-29, 2015, where we delivered presentations on Alzheimer's disease. Neurogranin was an upcoming fluid biomarker for which we had generated new monoclonal antibodies. Charles offered immediately to test these new antibodies in neuropathological staging of Alzheimer's disease.

    One year later we had our first joint paper accepted in Journal of Alzheimer's Disease (De Vos et al., 2016). In my opinion this not only illustrates Charles' commitment to deep insights into the science, but also toward advancing applications for the patient benefits.

    Like many, I will surely miss his drive and his inspiring way to move new insights into the science of brain diseases. My deepest sympathy goes to his family, friends and colleagues.

    References:

    De Vos A, Struyfs H, Jacobs D, Fransen E, Klewansky T, De Roeck E, Robberecht C, Van Broeckhoven C, Duyckaerts C, Engelborghs S, Vanmechelen E. The Cerebrospinal Fluid Neurogranin/BACE1 Ratio is a Potential Correlate of Cognitive Decline in Alzheimer's Disease. J Alzheimers Dis. 2016 Jul 6;53(4):1523-38. PubMed.

    View all comments by Eugeen Vanmechelen
    • User Profile Image Bart De Strooper
      UK Dementia Research Institute@UCL and VIB@KuLeuven
    • Posted:

    It is with deep sadness that I receive this news. Charles was a great scientist and a very kind colleague. We will miss him.

    View all comments by Bart De Strooper

  16. I knew Charles for many years, ever since I started my career as a young researcher in neuroscience. He was a brilliant and open-minded scientist and always happy to share his huge knowledge, to help and collaborate. I enjoyed many discussions and learned a lot from him over the years.

    I am very sad to hear that Charles has passed away and I will miss him very much.

    View all comments by Christian Czech

  17. What sad news. I was lucky enough to be welcomed at the Escourolle laboratory as a resident, and then as an assistant, from 2009 to 2011. I had the privilege of being introduced by Charles to his "dada", morphometry: I spent long, contemplative hours at the microscope, trying to apply the method of the optical dissector, at which he was excelling in practice. Charles Ducykaerts was the best at teaching one to observe, to see what must be seen, to deduce from one's observations a biological hypothesis to then be verified experimentally.

    Every morning at 8 a.m., 6 days a week, he was proceeding to the “wake-up as a morphologist,” which consisted of an educational reading session of slides from post-mortem cases. Privileged moments they were, sometimes a little stressful when the master was questioning the "students", with accuracy—and humor. Because the irrepressible humor of Professor Duyckaerts was also contributing to the pedagogy of these didactic sessions. His sense of irony stayed benevolent but always impactful!

    These sessions were also an opportunity to discover other facets of the mentor and Professor of Neuropathology. At the turn of the exchanges, with the modesty that characterized him in all areas, he proudly spoke of his family, his children, his wife.... and sometimes the most recent books he had read. This is how we discovered that he was a great lover of the novels of Virginie Despentes and her vitriolic writing style, maybe not that great a surprise.

    The scientific community, the patients, and his students will be missing Charles.

    View all comments by Virginie Desestret
    • User Profile Image Luc Buee
      Lille Neuroscience & Cognition
    • Posted:

    Charles Duyckaerts was born on 16 December 1951 in Liege, Belgium, and died on Saturday 6 August 2022 in Paris. He was a university professor-hospital practitioner. He directed the neuropathology laboratory on the Pitié Salpêtrière campus in Paris, France. He created and managed the National Brain Bank NeuroCEB since 2005. He was still a researcher in the Inserm team Alzheimer & Prion diseases at the ICM, a team he co-directed from 2009 to 2014. A member of various learned societies, Charles was secretary (1990-1994), then president (2009-2011) of the French Society of Neuropathology. He was affiliated to the French Society for Neuroscience (Société des Neurosciences) since its creation in 1988 and was a member of its board of directors from 2003 to 2007. He was invited by the Société des Neurosciences to give in 2018 the Alfred Fessard Lecture, the most prestigious lecture of this learned society.

    With a father and an uncle who were professors at the University of Liège, it was perhaps inevitable that Charles would embrace an academic career. He completed his medical studies and his theses (medicine and science) in France, but remained very attached to his country of birth and was a "corresponding" member of the Royal Academy of Medicine of Belgium. As an anatomopathologist and neurologist, Charles quickly became interested in neurodegenerative diseases. With Jean-Jacques Hauw, he was one of the pioneers in Alzheimer's research.

    As a neuropathologist, Charles believed what he saw: brain lesions. He rejected fads and defended his convictions. An ardent supporter of brain banks, he fought to encourage autopsies, and to have the interest that biological collections hold for research be better recognized. Even when genetics was chosen as a priority in the French presidential plans for Alzheimer's disease, he fought to find funding and enable a national register of brain banks. He was able to create vocations with the motivation of younger people, who are now flying on their own wings.

    Charles' involvement in neurodegenerative diseases enabled him to participate in several works defining the international criteria for anatomo-pathological diagnosis (Alzheimer's, corticobasal degeneration, fronto-temporal lobar degeneration, Parkinson's, etc). Thus, as early as 1985, he participated in meetings on the anatomopathological diagnosis of Alzheimer's disease, and then the new criteria in 1997 and 2011.

    In 2015, Charles opposed the creation of a new pathological entity called PART (primary age-related tauopathy) and published a position paper with experts in the field indicating the PART-Alzheimer's disease continuum (Duyckaerts et al., 2015). Recently, he participated in the neuropathological diagnostic criteria for progressive supranuclear palsy in conjunction with the Rainwater Charitable Foundation (Roemer et al., 2022).

    In his research, Charles has always been able to evolve with new methodological developments in his approaches (laser microdissection, confocal microscopy, stereology, tissue transparency (Clarity, 3DISCO). He believed what he saw, and he saw more and ever more ... Convinced that the histological approach does not allow one to approach all the components of the brain, Charles was interested in the lipids that disappear with the systems of fixative and treatment of tissues. He has thus shown the importance of cholesterol metabolism in Alzheimer's disease before the confirmations by genome-wide association studies (Girardot et al., 2003; Lebouvier et al., 2009 ).

    Charles Duyckaerts was the anatomo-pathologist who maintained that the laminar and regional distribution of neuropathological lesions allows us to better define the etiopathogenesis of diseases. The best example is his demonstration of the importance of cortico-cortical connections for the progression of tau pathology in Alzheimer's disease (Duyckaerts et al., 1997). This rigor allowed him to better characterize the experimental models.

    Charles was an internationally recognized expert in Alzheimer's and related disorders. It is not only at the Oscars that a Lifetime Achievement Award is given, since he received one in 2006 (Henry Wisniewski Prize awarded on the occasion of the International Congress on Alzheimer's Disease). He received many others, such as the IPSEN (1988) and Claude Pompidou (2011) awards for his research on Alzheimer's disease. More recently, in 2014, he was made Doctor Honoris Causa of the Catholic University of Leuven.

    Charles Duyckaerts contributed tirelessly to numerous organizations for the management, promotion and evaluation of research in France and internationally.

    On a personal note, Charles was my friend for almost 30 years. He was the rare scientist for whom only the search for truth mattered. Where the world of research features a fair amount of egocentricity, Charles was first and foremost about helping and sharing. I first met him as a young researcher. I had just returned from the United States, and our respective bosses were working together. Charles was first of all a mentor. He supported me in my career in the most difficult moments as well as in the successes. Over time, the mentor-mentee relationship disappeared in favor of friendship. Our knowledge was complementary, and that made us strong. We didn't publish much together but still we exchanged so much.

    Some subjects made us react, so we took up our pens and joined forces to defend a point of view or our hypotheses. In the last few months, some of us have been talking to Charles. I spoke with him in June. He remained philosophical, checking in with our mutual friends and talking about his life and his concerns for his loved ones. Although aware of his health, he was always optimistic about the future. I had promised Charles to come for a coffee but it all went too fast … One thing is certain: We feel a great void in our community. Alzheimerology has lost a researcher who had more integrity and was more collaborative than most. 

    Thank you, Charles.

    References:

    Duyckaerts C, Braak H, Brion JP, Buée L, Del Tredici K, Goedert M, Halliday G, Neumann M, Spillantini MG, Tolnay M, Uchihara T. PART is part of Alzheimer disease. Acta Neuropathol. 2015 May;129(5):749-56. Epub 2015 Jan 28 PubMed.

    Roemer SF, Grinberg LT, Crary JF, Seeley WW, McKee AC, Kovacs GG, Beach TG, Duyckaerts C, Ferrer IA, Gelpi E, Lee EB, Revesz T, White CL 3rd, Yoshida M, Pereira FL, Whitney K, Ghayal NB, Dickson DW. Rainwater Charitable Foundation criteria for the neuropathologic diagnosis of progressive supranuclear palsy. Acta Neuropathol. 2022 Oct;144(4):603-614. Epub 2022 Aug 10 PubMed.

    Girardot N, Allinquant B, Langui D, Laquerrière A, Dubois B, Hauw JJ, Duyckaerts C. Accumulation of flotillin-1 in tangle-bearing neurones of Alzheimer's disease. Neuropathol Appl Neurobiol. 2003 Oct;29(5):451-61. PubMed.

    Lebouvier T, Perruchini C, Panchal M, Potier MC, Duyckaerts C. Cholesterol in the senile plaque: often mentioned, never seen. Acta Neuropathol. 2009 Jan;117(1):31-4. PubMed.

    Duyckaerts C, Uchihara T, Seilhean D, He Y, Hauw JJ. Dissociation of Alzheimer type pathology in a disconnected piece of cortex. Acta Neuropathol. 1997 May;93(5):501-7. PubMed.

    View all comments by Luc Buee

  19. Charles had faith in what neuropathological observation could contribute to the advancement of neuroscience research. With great humanity, a lot of will and energy, he, in collaboration with patient associations, created the neuro-CEB brain tissue bank. He, who never bothered himself with useless discussions, liked to spend hours explaining the state of research to the general public, to the sick, to students of all levels. He was an exceptional teacher who drew the diagrams of his presentations freehand.

    View all comments by Danielle Seilhean

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References

News Citations

  1. Brain Anatomy Revealed With CLARITY

Paper Citations

  1. Duyckaerts C, Bennecib M, Grignon Y, Uchihara T, He Y, Piette F, Hauw JJ. Modeling the relation between neurofibrillary tangles and intellectual status. Neurobiol Aging. 1997 May-Jun;18(3):267-73. PubMed.
  2. Duyckaerts C. Looking for the link between plaques and tangles. Neurobiol Aging. 2004 Jul;25(6):735-9; discussion 743-6. PubMed.
  3. Panchal M, Loeper J, Cossec JC, Perruchini C, Lazar A, Pompon D, Duyckaerts C. Enrichment of cholesterol in microdissected Alzheimer's disease senile plaques as assessed by mass spectrometry. J Lipid Res. 2010 Mar;51(3):598-605. PubMed.
  4. Berr C, Hauw JJ, Delaère P, Duyckaerts C, Amouyel P. Apolipoprotein E allele epsilon 4 is linked to increased deposition of the amyloid beta-peptide (A-beta) in cases with or without Alzheimer's disease. Neurosci Lett. 1994 Sep 12;178(2):221-4. PubMed.
  5. Hauw JJ, Verny M, Delaère P, Cervera P, He Y, Duyckaerts C. Constant neurofibrillary changes in the neocortex in progressive supranuclear palsy. Basic differences with Alzheimer's disease and aging. Neurosci Lett. 1990 Nov 13;119(2):182-6. PubMed.
  6. Ando K, Laborde Q, Lazar A, Godefroy D, Youssef I, Amar M, Pooler A, Potier MC, Delatour B, Duyckaerts C. Inside Alzheimer brain with CLARITY: senile plaques, neurofibrillary tangles and axons in 3-D. Acta Neuropathol. 2014 Sep;128(3):457-9. Epub 2014 Jul 29 PubMed.
  7. Duyckaerts C, Sazdovitch V, Ando K, Seilhean D, Privat N, Yilmaz Z, Peckeu L, Amar E, Comoy E, Maceski A, Lehmann S, Brion JP, Brandel JP, Haïk S. Neuropathology of iatrogenic Creutzfeldt-Jakob disease and immunoassay of French cadaver-sourced growth hormone batches suggest possible transmission of tauopathy and long incubation periods for the transmission of Abeta pathology. Acta Neuropathol. 2018 Feb;135(2):201-212. Epub 2017 Nov 22 PubMed.
  8. Hervé D, Porché M, Cabrejo L, Guidoux C, Tournier-Lasserve E, Nicolas G, Adle-Biassette H, Plu I, Chabriat H, Duyckaerts C. Fatal Aβ cerebral amyloid angiopathy 4 decades after a dural graft at the age of 2 years. Acta Neuropathol. 2018 May;135(5):801-803. Epub 2018 Mar 5 PubMed.
  9. Duyckaerts C, Braak H, Brion JP, Buée L, Del Tredici K, Goedert M, Halliday G, Neumann M, Spillantini MG, Tolnay M, Uchihara T. PART is part of Alzheimer disease. Acta Neuropathol. 2015 May;129(5):749-56. Epub 2015 Jan 28 PubMed.

External Citations

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