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

Abstract

To explore the effects of donepezil on the activities of platelet α and β secretases in Alzheimer's disease (AD) patients. 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. 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. 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.