Hippocampal proteomic alteration in triple transgenic mouse model of Alzheimer’s disease and implication of PINK 1 regulation in donepezil treatment

ABSTRACT Background: Donepezil is a clinically approved acetylcholinesterase inhibitor (AChEI) for cognitive improvement in Alzheimer’s disease (AD). Donepezil has been used as a first-line therapeutics for the symptomatic treatment of AD, but its ability to modify disease pathology and underlying mechanisms are not clear. Methods: We investigated the protective effects and underlying mechanisms of donepezil in AD-related triple transgenic (APPSwe/PSEN1M146V/MAPTP301L) mouse model (3×Tg-AD). Mice (8-month old) were treated with donepezil (1.3 mg/kg) for 4 months and evaluated by behavioral tests for assessment of cognitive functions and the hippocampal tissues were examined by protein analysis and quantitative proteomics. Results: Behavioral tests showed that donepezil significantly improved the cognitive capabilities of 3xTg-AD mice. The levels of soluble and insoluble amyloid beta proteins (Aβ1-40 and Aβ1-42) and senile plaques were reduced in the hippocampus. Golgi staining of the nervous tissue showed...