11597 RESULTS
COMMENT Zheng et al. report a novel method, analyzing TEM micrographs of plasma HDL particles with a deep learning model, to measure diameters of individual HDL particles derived from a cohort of 183 participants stratified by cognitive status. This report provid
COMMENT This study makes a valuable contribution to the search for fluid biomarkers in FTD. By investigating the CSF proteome in the well-characterized GENFI cohort, the authors analyzed a large group of presymptomatic and symptomatic carriers of mutations relate
COMMENT This work is a tour de force, with a series of well-planned studies examining soluble tau assemblies (STAs) using a FRET assay in which both components are the same antibody, although the exact antibody used is not clear from the manuscript. The authors d
COMMENT This contains encouraging findings about the identification of phosphotau species that may correlate with pretangles and be a marker of risk for progression of AD-related cognitive decline. If replicated and expanded, these findings could provide importan
COMMENT This beautiful work uses human brain samples, particularly the FRET assay showing that there are soluble tau oligomers, named “soluble tau assemblies.” It is puzzling to see that these STAs are AD specific! For the CSF analyses, I am less convinced of the
COMMENT Tau pathology in humans or animals, without fail, is made up of the hyperphosphorylated protein. In AD tau is hyperphosphorylated sub-stoichiometrically at multiple sites by several combinations of protein kinases. Six isoforms of tau in the human brain a
COMMENT This study represents a significant step forward in understanding early tau pathology and advancing biomarker development for AD. The identification of phosphorylation at serine-262 and serine-356 within the soluble tau assembly (STA) core (~tau258–368) p
COMMENT This study is impactful because soluble tau assemblies (STA) containing phospho-tau serine-262 and phospho-tau-serine-356 were identified as components of pre-tangles, which are precursors of insoluble neurofibrillary tangles. From previous Cryo-EM experi
COMMENT This interesting paper follows 30 years of the highly reproduced finding that the quantity of Aβ extracted from AD cortex in aqueous buffer, and retained in the supernatant after centrifugation (here termed protofibrils), correlates better with cognitive
COMMENT In this study Wu et al. make an important contribution to a trajectory of recent papers on the damaging role of lipid-droplet-accumulating microglia (LDAM). In 2020, transcriptomic and functional studies of LDAM in the aged mouse brain established this mi
COMMENT To some extent, repeat expansions have been the dark matter of human disease. They are generally missed by SNP arrays and by short-read sequencing technologies and it is only with long-read sequencing we can see them and also appreciate their high mutatio
COMMENT In this new study by Kedia et al. their imaging pipeline is quite similar to our previous work based on our 2021 paper (Cai and Tai, 2024; Bhattacharya et al., 2021). The imaging resolution is about the same in their and our study because the imaging prin
COMMENT This is an important study for fluid biomarker development in FTD. The results could support further diagnostic and therapeutic development in FTD, a condition with no cure and for which no specific diagnostic test exist. The study in this European cohort
COMMENT This is a very impactful paper. The authors found distinct and shared proteomic alterations across genetic FTD subtypes. Each genetic FTD mutation (C9ORF72, GRN, MAPT) displayed unique CSF proteomic changes. Some proteins were altered across all three sub
COMMENT This is impressive work. The relatively large number of individuals per genetic subtype included explains the large number of proteins identified. The paper is a very valuable source for other proteomics studies. There are not so many proteomics studies p
