Exploring the connection between dementia and cardiovascular risk with a focus on ADAM10

Author(s)

Targas, Ana Beatriz Aparecida ; Victoriano, Pedro Henrique Moreira ; Garcia, Mateus Balleiro Bertoldo ; Alexandre-Silva, Vanessa ; Cominetti, Marcia Regina

• Document type: Journal article
• Source: BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE; v. 1871, n. 5, p. 12-pg., 2025-06-01.

Abstract

Alzheimer's disease (AD) represents a leading cause of dementia, characterized by progressive cognitive and functional decline. Although extensive research has unraveled critical aspects of AD pathology, its etiology remains incompletely understood, urging further exploration into potential risk factors. Growing evidence underscores a significant link between cardiovascular disease (CVD) risk factors and AD, with modifiable lifestyle elements - such as physical inactivity, high low-density lipoprotein (LDL) levels, obesity, hypertension, atherosclerosis, and diabetes - emerging as contributors to cerebrovascular damage and neurodegeneration. ADAM10, a disintegrin and metalloproteinase involved in the non-amyloidogenic processing of amyloid precursor protein (APP), has garnered interest for its dual role in cardiovascular and neurodegenerative processes. ADAM10's regulation of neuroinflammation, endothelial function, and proteolytic cleavage of APP potentially moderates amyloid-beta (A beta) peptide formation, thus influencing both cardiovascular and brain health. Given these interconnected roles, this narrative review investigates whether ADAM10-driven vascular dysfunction accelerates neurodegeneration, how lipid metabolism influences ADAM10 activity in CVD and AD, and whether targeting ADAM10 could offer a dual-benefit therapeutic strategy to mitigate disease burden. By exploring epidemiological data, clinical studies, and molecular pathways, we aim to clarify ADAM10's bridging function between AD and cardiovascular risk, offering a new perspective into therapeutic opportunities to alleviate the dual burden of these interrelated conditions. (AU)

• FAPESP's process: 24/05940-6 - Effects of Low Density Lipoprotein (LDL) Treatment on ADAM10 Expression in Neuronal and Endothelial Cells: A Molecular Investigation of Modifiable Risk Factors for Dementia
• Grantee: Ana Beatriz Aparecida Targas
• Support Opportunities: Scholarships in Brazil - Master
• FAPESP's process: 24/03123-0 - Association between LDL cholesterol levels and ADAM10 in carriers and non-carriers of the APOE e4 allele
• Grantee: Mateus Balleiro Bertoldo Garcia
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• FAPESP's process: 21/01863-9 - Biology and function of ADAM10 isoforms for differential diagnosis of Alzheimer's Disease by electrochemical sensors
• Grantee: Márcia Regina Cominetti
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 21/14673-3 - Multi-user equipment approved in grant 2021/01863-9: Real time PCR system QuantStudio qPCR
• Grantee: Márcia Regina Cominetti
• Support Opportunities: Multi-user Equipment Program
• FAPESP's process: 23/00449-0 - Levels and activity of ADAM10, an Alzheimers disease serum biomarker, in different cellular compartments
• Grantee: Vanessa Alexandre da Silva
• Support Opportunities: Scholarships in Brazil - Master
• FAPESP's process: 23/17574-1 - Association between ADAM10 levels and cardiovascular risk in cognitively healthy adults
• Grantee: Pedro Henrique Moreira Victoriano
• Support Opportunities: Scholarships in Brazil - Scientific Initiation