Annexin A6 membrane repair protein protects against amyloid-induced dystrophic neurites and tau phosphorylation in Alzheimer's disease model mice.

ABSTRACT: In Alzheimer's disease, accumulation of amyloid-β (Aβ) peptide is thought to cause formation of neurofibrillary tangles composed of hyperphosphorylated tau protein, which correlates with neuronal loss and cognitive impairment, but the mechanism linking Aβ and tau pathologies is unknown. Dystrophic neurites, which surround Aβ plaques and accumulate phosphorylated tau and other proteins, may play a role in seeding and spreading of pathologic tau. Here, we investigate the novel hypothesis that improved membrane repair capacity decreases dystrophic neurite formation by protecting axons from Aβ-induced membrane damage. Using a ratiometric calcium sensor and a FRET-based calpain cleavage sensor, we demonstrate that dystrophic neurites in 5XFAD mice have elevated resting calcium levels and calpai

SUBMITTER: Sadleir KR 

PROVIDER: S-EPMC12103342 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature