ADAM10 Plasma and CSF Levels Are Increased in Mild Alzheimer's Disease

Autor(es):Mostrar menos -

Pereira Vatanabe, Izabela ^[1] ; Peron, Rafaela ^[1] ; Mantellatto Grigoli, Marina ^[1] ; Pelucchi, Silvia ^[2] ; De Cesare, Giulia ^[2] ; Magalhaes, Thamires ^[3] ; Manzine, Patricia Regina ^[1] ; Figueredo Balthazar, Marcio Luiz ^[3] ; Di Luca, Monica ^[2] ; Marcello, Elena ^[2] ; Cominetti, Marcia Regina ^[1]

Afiliação do(s) autor(es)

^[1] Univ Fed Sao Carlos, Dept Gerontol, BR-13565905 Sao Carlos - Brazil

^[2] Univ Milan, Dept Pharmacol & Biomol Sci, I-20133 Milan - Italy

^[3] Univ Estadual Campinas, Dept Neurol, BR-13083887 Campinas - Brazil

• Tipo de documento: Artigo Científico
• Fonte: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES; v. 22, n. 5 MAR 2021.
• Citações Web of Science: 1

Resumo

ADAM10 is the main alpha-secretase that participates in the non-amyloidogenic cleavage of amyloid precursor protein (APP) in neurons, inhibiting the production of beta-amyloid peptide (A beta) in Alzheimer's disease (AD). Strong recent evidence indicates the importance of the localization of ADAM10 for its activity as a protease. In this study, we investigated ADAM10 activity in plasma and CSF samples of patients with amnestic mild cognitive impairment (aMCI) and mild AD compared with cognitively healthy controls. Our results indicated that plasma levels of soluble ADAM10 were significantly increased in the mild AD group, and that in these samples the protease was inactive, as determined by activity assays. The same results were observed in CSF samples, indicating that the increased plasma ADAM10 levels reflect the levels found in the central nervous system. In SH-SY5Y neuroblastoma cells, ADAM10 achieves its major protease activity in the fraction obtained from plasma membrane lysis, where the mature form of the enzyme is detected, confirming the importance of ADAM10 localization for its activity. Taken together, our results demonstrate the potential of plasma ADAM10 to act as a biomarker for AD, highlighting its advantages as a less invasive, easier, faster, and lower-cost processing procedure, compared to existing biomarkers. (AU)

• Processo FAPESP: 19/02648-4 - Papel de proteínas da via de sinalização da insulina e sua relação com a secretase ADAM10 na Doença de Alzheimer
• Beneficiário: Márcia Regina Cominetti
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 16/06226-9 - ADAM10 como biomarcador de fragilidade cognitiva
• Beneficiário: Izabela Pereira Vatanabe
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 15/26084-1 - Avaliação da ADAM10 plaquetária em demências não-Alzheimer
• Beneficiário: Patricia Regina Manzine Moralles
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado