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

Biochim Biophys Acta Mol Basis Dis. 2025 Mar 31:167825. doi: 10.1016/j.bbadis.2025.167825. Online ahead of print.

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 risk factors and AD, with modifiable lifestyle elements - such as physical inactivity, high 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, 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 Aβ 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.

PMID:40174790 | DOI:10.1016/j.bbadis.2025.167825