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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Protein Expression of BACE1 is Downregulated by Donepezil in Alzheimer's Disease Platelets

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Author(s):
Sarno, Tamires Alves ; Talib, Leda Leme ; Giroud Joaquim, Helena Passarelli ; de Franca Bram, Jessyka Maria ; Gattaz, Wagner Farid ; Forlenza, Orestes Vicente
Total Authors: 6
Document type: Journal article
Source: JOURNAL OF ALZHEIMER'S DISEASE; v. 55, n. 4, p. 1445-1451, 2017.
Web of Science Citations: 2
Abstract

Background: Abnormal amyloid-beta protein precursor (A beta PP) metabolism is a key feature of Alzheimer's disease (AD). Platelets contain most of the enzymatic machinery required for A beta PP processing, and correlates of intracerebral abnormalities have been demonstrated in platelets of patients with AD. Thus, A beta PP-related molecules in platelets may be regarded as peripheral markers of AD. Objective: We sought to determine the protein expression of the A beta PP secretases (ADAM10, BACE1, and PSEN1) and A beta PP 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 A beta PP 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 A beta PP 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. (AU)

FAPESP's process: 13/20695-3 - Effect of cholinesterase inhibitor on APP metabolism in platelets
Grantee:Tamires Alves Sarno
Support Opportunities: Scholarships in Brazil - Master
FAPESP's process: 09/52825-8 - Neurobiology of Alzheimer's disease: risk markers, prognosis and therapeutic response
Grantee:Wagner Farid Gattaz
Support Opportunities: Research Projects - Thematic Grants