biostudies-literatureJean LSynaptica Ltd.6253-6272https://www.ebi.ac.uk/biostudies/studies/S-EPMC6484111biostudies-literatureUnknown294(16)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 <i>in vitro</i> and Aβ deposition and toxicity <i>in vivo</i> Only hAChE-S contains an amphiphilic C-terminal dThe Journal of biological chemistry<i>In vivo</i> localization of human acetylcholinesterase-derived species in a β-sheet conformation at the core of senile plaques in Alzheimer's disease.PMC6484111AChE peptideJean LBrimijoin SVaux DJfalse<i>In vivo</i> localization of human acetylcholinesterase-derived species in a β-sheet conformation at the core of senile plaques in Alzheimer's disease.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 <i>in vitro</i> and Aβ deposition and toxicity <i>in vivo</i> Only hAChE-S contains an amphiphilic C-terminal d2019-01-01T00:00:00Z2019 Apr2025-05-29T20:47:44.393Z2025-05-29T20:47:44.393ZS-EPMC64841113078710210.1074/jbc.ra118.00623010.1074/jbc.RA118.006230