8BGV

Tau Paired Helical Filament from Cellular Fraction of Alzheimer's disease brain

Summary for 8BGV

• Entry DOI: 10.2210/pdb8bgv/pdb
• EMDB information: 16039
• Descriptor: Microtubule-associated protein tau (1 entity in total)
• Functional Keywords: protein fibril, amyloid
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 7
• Total formula weight: 321439.10

Authors

Behr, T.S.,Ryskeldi-Falcon, B. (deposition date: 2022-10-28, release date: 2023-05-24, Last modification date: 2024-07-24)

Primary citation

Fowler, S.L.,Behr, T.S.,Turkes, E.,Cauhy, P.M.,Foiani, M.S.,Schaler, A.,Crowley, G.,Bez, S.,Ficulle, E.,Tsefou, E.,O'Brien, D.P.,Fischer, R.,Geary, B.,Gaur, P.,Miller, C.,D'Acunzo, P.,Levy, E.,Duff, K.E.,Ryskeldi-Falcon, B.
Tau filaments are tethered within brain extracellular vesicles in Alzheimer's disease.
Biorxiv, 2023

PubMed Abstract: The abnormal assembly of tau protein in neurons is the pathological hallmark of multiple neurodegenerative diseases, including Alzheimer's disease (AD). In addition, assembled tau associates with extracellular vesicles (EVs) in the central nervous system of patients with AD, which is linked to its clearance and prion-like propagation between neurons. However, the identities of the assembled tau species and the 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 AD patients. We found filaments of truncated tau enclosed within EVs enriched in endo-lysosomal proteins. We observed multiple filament interactions, including with molecules that tethered filaments to the EV limiting membrane, suggesting selective packaging. Our findings will guide studies into the molecular mechanisms of EV-mediated secretion of assembled tau and inform the targeting of EV-associated tau as potential therapeutic and biomarker strategies for AD.

PubMed: 37163117
DOI: 10.1101/2023.04.30.537820

Experimental method

ELECTRON MICROSCOPY (3.27 Å)