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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 levels of ADAM10, BACE1, and PSEN1 in platelets and leukocytes of Alzheimer's disease patients

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Autor(es):
Bram, Jessyka Maria de Franca [1] ; Talib, Leda Leme [1] ; Joaquim, Helena Passarelli Giroud [1] ; Sarno, Tamires Alves [1] ; Gattaz, Wagner Farid [1] ; Forlenza, Orestes Vicente [1]
Número total de Autores: 6
Afiliação do(s) autor(es):
[1] Univ Sao Paulo, Dept & Inst Psiquiatria, Lab Neurociencias LIM 27, HCFMUSP, Fac Med, Rua Doutor Ovidio Pires de Campos 785, BR-05403010 Sao Paulo, SP - Brazil
Número total de Afiliações: 1
Tipo de documento: Artigo Científico
Fonte: EUROPEAN ARCHIVES OF PSYCHIATRY AND CLINICAL NEUROSCIENCE; v. 269, n. 8, p. 963-972, DEC 2019.
Citações Web of Science: 2
Resumo

The clinical diagnosis of Alzheimer's disease (AD) is a probabilistic formulation that may lack accuracy particularly at early stages of the dementing process. Abnormalities in amyloid-beta precursor protein (APP) metabolism and in the level of APP secretases have been demonstrated in platelets, and to a lesser extent in leukocytes, of AD patients, with conflicting results. The aim of the present study was to compare the protein level of the APP secretases A-disintegrin and metalloprotease 10 (ADAM10), Beta-site APP-cleaving enzyme 1 (BACE1), and presenilin-1 (PSEN1) in platelets and leukocytes from 20 non-medicated older adults with AD and 20 healthy elders, and to determine the potential use of these biomarkers to discriminate cases of AD from controls. The protein levels of all APP secretases were significantly higher in platelets compared to leukocytes. We found statistically a significant decrease in ADAM10 (52.5%, p < 0.0001) and PSEN1 (32%, p = 0.02) in platelets from AD patients compared to controls, but not in leukocytes. Combining all three secretases to generate receiver-operating characteristic (ROC) curves, we found a good discriminatory effect (AD vs. controls) when using platelets (the area under the curve-AUC-0.90, sensitivity 88.9%, specificity 66.7%, p = 0.003), but not in leukocytes (AUC 0.65, sensitivity 77.8%, specificity 50.0%, p = 0.2). Our findings indicate that platelets represent a better biological matrix than leukocytes to address the peripheral level of APP secretases. In addition, combining the protein level of ADAM10, BACE1, and PSEN1 in platelets, yielded a good accuracy to discriminate AD from controls. (AU)

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