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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

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

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Autor(es):
Sarno, Tamires Alves ; Talib, Leda Leme ; Giroud Joaquim, Helena Passarelli ; de Franca Bram, Jessyka Maria ; Gattaz, Wagner Farid ; Forlenza, Orestes Vicente
Número total de Autores: 6
Tipo de documento: Artigo Científico
Fonte: JOURNAL OF ALZHEIMER'S DISEASE; v. 55, n. 4, p. 1445-1451, 2017.
Citações Web of Science: 2
Resumo

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)

Processo FAPESP: 09/52825-8 - Neurobiologia da doença de Alzheimer: marcadores de risco, prognóstico e resposta terapêutica
Beneficiário:Wagner Farid Gattaz
Linha de fomento: Auxílio à Pesquisa - Temático
Processo FAPESP: 13/20695-3 - Efeito de inibidor da colinesterase no metabolismo da APP em plaquetas
Beneficiário:Tamires Alves Sarno
Linha de fomento: Bolsas no Brasil - Mestrado