Distinct populations of highly potent TAU seed conformers in rapidly progressing Alzheimer's disease.

ABSTRACT: Although genetic factors play a main role in determining the risk of developing Alzheimer’s disease (AD), they do not explain extensive spectrum of clinicopathological phenotypes. Deposits of aggregated TAU proteins are one of the main predictors of cognitive decline in AD. We investigated the hypothesis that variabilities in AD progression could be due to diverse structural assemblies (strains) of TAU protein. Using sensitive biophysical methods in 40 patients with AD and markedly different disease durations, we identified populations of distinct TAU particles that differed in size, structural organization, and replication rate in vitro and in cell assay. The rapidly replicating, distinctly misfolded TAU conformers found in rapidly progressive AD were composed of ~80% misfolded four-repea

SUBMITTER: Kim C 

PROVIDER: S-EPMC9549419 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature