11586 RESULTS
COMMENT Benjamin Ryskeldi-Falcon, Diane Arseni, and colleagues have extended their fantastic cryo-EM work in TDP-43 proteinopathies. After reporting the first structure of TDP-43 filaments in ALS/FTLD-TDP type B cases last year (Arseni et al., 2022), in this stud
COMMENT For decades, the link between Lewy body (LB) pathology with parkinsonism and cognitive impairment has been known. Most commonly LB pathology clinically manifests as Parkinson’s disease dementia or dementia with Lewy bodies. Subsequent studies have highlig
COMMENT The remarkable ability of seed amplification assays (SAA), such as RT-QuIC, to detect pathological α-synuclein in CSF has enabled many interesting clinical questions to be addressed, in particular, those related to early diagnosis of synuclein disorders.
COMMENT Evidence indicates that APOE Christchurch plays a protective role by disrupting the connection between APOE and HSPG. This disruption, in turn, leads to a reduction in tau phosphorylation at S396—a significant and pathological phospho-tau site associated
COMMENT The series of papers related to the ApoE3-Christchurch mutation from Drs. Arboleda-Velasquez and Quiroz, is a clear example of how a case report of a single-residue mutation (Nov 2019 news; Sepulveda-Falla et al., 2022) might help to, first, understand pa
COMMENT The presentation by Dr. Quiroz at the featured research symposium organized by the atypical AD PIA was one of our personal highlights of AAIC. The talk covered the previous discovery of an individual from a large kindred living in the region of Paisa in C
COMMENT Building on the strength of CSF seed amplification assays for α-synuclein, there are now several efforts underway to biologically define and stage Lewy body disease, including PD, PD dementia, and dementia with Lewy bodies (DLB). These efforts represent a
COMMENT I think this is an extremely important and exciting study. It would be great to see additional brains analyzed to learn more about earlier disease stages, in contrast to late-stage disease reported in this study, and to explore if these findings can be re
COMMENT This study is exciting because it reproduced in human postmortem AD brain tissue prior findings from mouse models, showing the accumulation of extracellular vesicles (EVs), as well as lipid droplets and different form of amyloid fibrils, in amyloid plaque
COMMENT First authors Madeleine Gilbert, Nayab Fatima, Joshua Jenkins, and Thomas O’Sullivan, from the group of René Frank at the University of Leeds, have pioneered the use of electron cryo-tomography (cryo-ET) to image Aβ and tau pathology at molecular resoluti
COMMENT This preprint by Gilbert, Fatima, Jenkins, O'Sullivan et al. from the group of René Frank at the University of Leeds describes the first-ever use of electron cryo-tomography (cryo-ET) on high-pressure frozen brain tissue (temporal cortex) from an ind
COMMENT Frank and colleagues now extend their beautiful cryo-ET work in mouse models to postmortem human Alzheimer’s disease brain with largely similar results. This work goes beyond the plastic-embedded, negative-staining EM begun in the last century to show us
COMMENT The Michael J. Fox Foundation has supported α-synuclein PET tracer development for over a decade and has funded more than $30 million in research. It is likely that a tracer will need to be highly selective with minimal binding to other targets including
COMMENT The impetus for LEADS is twofold. First, we think sporadic early onset Alzheimer’s disease (EOAD) is an ideal population for AD trials and drug development. They have fewer co-pathologies, so AD is driving clinical decline. Biomarkers and clinical outcome
COMMENT This Nature Medicine article nicely supports incorporating measurements of CSF levels of MTBR-tau as a potential biomarker for tau tangle pathology in AD. It is notable, though, that MTBR-tau in CSF was recently shown to be decreased in primary tauopathie
