In vivo localization of human acetylcholinesterase-derived species in a β-sheet conformation at the core of senile plaques in Alzheimer's disease.

ABSTRACT: Many neurodegenerative diseases are characterized by amyloid deposition. In Alzheimer's disease (AD), β-amyloid (Aβ) peptides accumulate extracellularly in senile plaques. The AD amyloid cascade hypothesis proposes that Aβ production or reduced clearance leads to toxicity. In contrast, the cholinergic hypothesis argues for a specific pathology of brain cholinergic pathways. However, neither hypothesis in isolation explains the pattern of AD pathogenesis. Evidence suggests that a connection exists between these two scenarios: the synaptic form of human acetylcholinesterase (hAChE-S) associates with plaques in AD brains; among hAChE variants, only hAChE-S enhances Aβ fibrillization in vitro and Aβ deposition and toxicity in vivo Only hAChE-S contains an amphiphilic C-terminal d

SUBMITTER: Jean L 

PROVIDER: S-EPMC6484111 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature