Tau filaments are tethered within brain extracellular vesicles in Alzheimer's disease.

ABSTRACT: The abnormal assembly of tau protein in neurons is a pathological hallmark of multiple neurodegenerative diseases, including Alzheimer's disease (AD). Assembled tau associates with extracellular vesicles (EVs) in the central nervous system of individuals with AD, which is linked to its clearance and prion-like propagation. However, the identities of the assembled tau species and EVs, as well as how they associate, are not known. Here, we combined quantitative mass spectrometry, cryo-electron tomography and single-particle cryo-electron microscopy to study brain EVs from individuals with AD. We found tau filaments composed mainly of truncated tau that were enclosed within EVs enriched in endo-lysosomal proteins. We observed multiple filament interactions, including with molecules that tethe

SUBMITTER: Fowler SL 

PROVIDER: S-EPMC11706778 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature