APOE isoform-associated tau oligomer polymorphs differ in synaptotoxicity and seeding activity.

ABSTRACT:

Introduction

Pathological tau aggregates form distinct polymorphic species across diseases and even across Alzheimer's disease (AD) patients. However, tau aggregate polymorphism across the apolipoprotein E isoforms (APOE ε2, ε3, ε4), the strongest predictors of late-onset AD development, is unknown.

Methods

This study assessed the conformational and bioactivity properties of tau oligomers from 14 patients with varying APOE genotypes.

Results

Tau oligomers differ in proteolytic stability and cleavage site profiles across the APOE isoforms, indicating conformationally distinct polymorphs. APOE isoform-associated tau oligomers affect synaptic plasticity differently, with ε4-associated oligomers having the highest potency and strongest impact on synaptic functioning. Bioa

SUBMITTER: Moreno N 

PROVIDER: S-EPMC12701364 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature