Proteomic polygenic risk scores of age-related plasma protein levels reveal a role for Metalloproteinase inhibitor 2 (TIMP2) in cognitive performance.

ABSTRACT: Several studies in mice have identified blood proteins that influence brain aging, yet translating these findings into humans remains challenging. To address this gap, we conducted a systematic review that identified 12 proteins reported to have an aging or rejuvenating effect in murine brains. Using protein quantitative trait loci data, we computed proteomic polygenic risk scores (protPRSs) capturing the lifelong genetic predisposition to higher or lower plasma protein levels and their regulation. We first validated the prediction accuracy of these protPRSs in two independent cohorts: 10 protPRSs in the Knight-ADRC and 7 protPRSs in the ALFA+ cohort significantly predicted their corresponding protein levels, although effect sizes were modest. We then examined their association with cognit

SUBMITTER: Anastasi F 

PROVIDER: S-EPMC12646536 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature