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

Author(s):Show less -

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]

Affiliation

^[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

• Document type: Journal article
• Source: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES; v. 22, n. 5 MAR 2021.
• Web of Science Citations: 1

Abstract

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)

• FAPESP's process: 19/02648-4 - Role of the insulin signaling pathway proteins and their relation with the secretase ADAM10 in Alzheimer's Disease
• Grantee: Márcia Regina Cominetti
• Support Opportunities: Regular Research Grants
• FAPESP's process: 16/06226-9 - ADAM10 as a cognitive frailty biomarker
• Grantee: Izabela Pereira Vatanabe
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 15/26084-1 - Evaluation of platelet ADAM10 in non-Alzheimer's dementias
• Grantee: Patricia Regina Manzine Moralles
• Support Opportunities: Scholarships in Brazil - Post-Doctoral