Swedish Alzheimer's disease variant perturbs activity of retrograde molecular motors and causes widespread derangement of axonal transport pathways.

ABSTRACT: Experimental studies in flies, mice, and humans suggest a significant role of impaired axonal transport in the pathogenesis of Alzheimer's disease (AD). The mechanisms underlying these impairments in axonal transport, however, remain poorly understood. Here we report that the Swedish familial AD mutation causes a standstill of the amyloid precursor protein (APP) in the axons at the expense of its reduced anterograde transport. The standstill reflects the perturbed directionality of the axonal transport of APP, which spends significantly more time traveling in the retrograde direction. This ineffective movement is accompanied by an enhanced association of dynactin-1 with APP, which suggests that reduced anterograde transport of APP is the result of enhanced activation of the retrograde mole

SUBMITTER: Feole M 

PROVIDER: S-EPMC10997842 | biostudies-literature | 2024 Mar

REPOSITORIES: biostudies-literature