Tau reduction prevents Aβ-induced axonal transport deficits by blocking activation of GSK3β.

ABSTRACT: Axonal transport deficits in Alzheimer's disease (AD) are attributed to amyloid β (Aβ) peptides and pathological forms of the microtubule-associated protein tau. Genetic ablation of tau prevents neuronal overexcitation and axonal transport deficits caused by recombinant Aβ oligomers. Relevance of these findings to naturally secreted Aβ and mechanisms underlying tau's enabling effect are unknown. Here we demonstrate deficits in anterograde axonal transport of mitochondria in primary neurons from transgenic mice expressing familial AD-linked forms of human amyloid precursor protein. We show that these deficits depend on Aβ1-42 production and are prevented by tau reduction. The copathogenic effect of tau did not depend on its microtubule binding, interactions with Fyn, or potential role in ne

SUBMITTER: Vossel KA 

PROVIDER: S-EPMC4427789 | biostudies-literature | 2015 May

REPOSITORIES: biostudies-literature