Affiliations: Laboratory of Neuroscience (LIM-27), Department and Institute of Psychiatry, Faculty of Medicine, University of São Paulo (USP), Sao Paulo, Brazil
Correspondence:
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Correspondence to: Orestes V. Forlenza and Tamires Alves Sarno, Laboratory of Neuroscience (LIM-27), Instituto de Psiquiatria do Hospital das Clínicas da Faculdade de Medicina da USP, Rua Doutor Ovídio Pires de Campos 785, CEP 05403-010, São Paulo, SP, Brazil. Tel.: +55 11 2661 7283; Fax: +55 11 2661 7535; E-mail: forlenza@usp.br (O.V. Forlenza); tamires_alvesbs@hotmail.com (T.A. Sarno).
Abstract: Background: Abnormal amyloid-β protein precursor (AβPP) metabolism is a key feature of Alzheimer’s disease (AD). Platelets contain most of the enzymatic machinery required for AβPP processing, and correlates of intracerebral abnormalities have been demonstrated in platelets of patients with AD. Thus, AβPP-related molecules in platelets may be regarded as peripheral markers of AD. Objective: We sought to determine the protein expression of the AβPP secretases (ADAM10, BACE1, and PSEN1) and AβPP ratio in platelets of patients with mild or moderate AD compared to healthy controls. We further determined whether the protein expression of these markers might be modified by chronic treatment with donepezil. Methods: Platelet samples were obtained from patients and controls at baseline and after 3 and 6 months of continuous treatment with therapeutic doses of donepezil. The protein expression of platelet markers was determined by western blotting. Results: AD patients had a significant decrease in AβPP ratio, ADAM10, and PSEN1 compared to controls at baseline, but these differences were not modified by the treatment. Nonetheless, a significant reduction in the protein expression of BACE1 was observed in patients treated with donepezil for 6 months. Conclusion: Our results corroborate previous findings from our group and others of decreased AβPP ratio and protein expression of ADAM10 in AD. We further show that PSEN1 is decreased in AD platelets, and that the protein expression of BACE1 is downregulated by chronic treatment with donepezil. This effect may be interpreted as evidence of disease modification.
