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Effects of donepezil treatment on platelets α and β secretase activities in Alzheimer’s disease patients

Authors

Dong, Gen-shan, Li, Xue, Jiang, Qiu-huan, Yang, Hong-qi

Journal

Zhonghua Yi Xue Za Zhi, Volume: 91, No.: 47, Pages.: 3341-3345

Year of Publication

2011

Abstract

Objective: To explore the effects of donepezil on the activities of platelet α and β secretases in Alzheimer’s disease (AD) patients.; Methods: During the period of 2007 – 2010, a total of 76 AD patients received either regular treatment alone or in combination with donepezil (5 mg/d) for a 12-week period. And their effects on ADAS-Cog (Alzheimer’s disease assessment scale-cognitive subscale) total and ADL (activity of daily living) scores were measured. The effects of donepezil on α and β secretase activities and sAPPα (soluble amyloid precursor protein α) secretion in AD patients and non-demented patients were detected by fluorescence and Western blot respectively.; Results: After the donepezil treatment, the ADAS-Cog scores of the treatment group decreased versus the control [(5.3 ± 4.4) vs (1.7 ± 1.6)]. And the differences were statistically significant (P < 0.01). And the ADL scores of the treatment group decreased versus the control [(41 ± 7) vs. (48 ± 6)]. And the differences were statistically significant (P < 0.05). As compared with that of pre-treatment (50 ± 6), the differences were statistically significant (P < 0.05). The activity of α secretase increased markedly while that of β secretase decreased markedly versus the controls [(91% ± 9%) vs (64% ± 8%), P < 0.01; (119% ± 11%) vs (178% ± 17%), P < 0.01]. Both had significant statistical differences with those of pre-treatment (both P < 0.01). As compared with the non-demented group (100% ± 12%, P < 0.001), the sAPPα contents of treatment and control groups were (64% ± 14%, P < 0.01) and (26% ± 8%, P < 0.001) respectively.; Conclusion: The administration of donepezil in AD patients improves cognitive functions and daily activities as indicated by the decreased ADAS-Cog total scores and ADL scores through the increased activity of α secretase and the decreased activity of β secretase. The clinical efficacy of donepezil may be attributed to its pharmacological effects on the regulation of platelet secretase activities.;

Keywords

aged, aged, 80 and over, alzheimer disease, amyloid precursor protein secretases, blood platelets, cholinesterase inhibitors, donepezil, drug therapy, enzymology, female, humans, indans, male, metabolism, piperidines, therapeutic use, treatment outcome

Countries of Study

China

Types of Dementia

Alzheimer’s Disease

Types of Study

Non randomised controlled trial

Type of Outcomes

ADLs/IADLs, Cognition

Type of Interventions

Pharmaceutical Interventions

Pharmaceutical Interventions

Anti-Alzheimer medications, e.g.: donezepil, galantamine, rivastigmine, memantime