Seed structure and phosphorylation in the fuzzy coat impact tau seeding competency.

ABSTRACT: Tau misfolding into β-sheet-rich filaments and subsequent recruitment of monomeric tau are central to Alzheimer's disease (AD) pathogenesis. While cryo-EM has resolved the conformation of the AD tau core, the structural features conferring biological activity remain unclear. Here, we investigated how tau filament core structure and post-translational modifications influence seeding capacity in neurons and mice. Our findings show that although filament structure impacts seeding, the AD tau core alone is insufficient to fully replicate AD tau's biological activity. The unstructured fuzzy coat, particularly phosphorylation within this region, is essential for full seeding competence. Importantly, recombinant tau filaments bearing twelve phospho-mimetic residues (PAD12 tau) and adopting the AD

SUBMITTER: Kasen A 

PROVIDER: S-EPMC12534512 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature