Biological age acceleration associates with Alzheimer's disease plasma biomarker levels

INTRODUCTION: Epigenetic clocks associate with neuropathology and Alzheimer's disease (AD) clinical risk, but findings are mixed regarding whether clocks associate with blood-based biomarkers and in non-European populations. METHODS: We calculated biological age and age acceleration from blood methylation data in 704 older Hispanic adults and tested associations with clinical diagnosis and antemortem biomarker levels. RESULTS: Age acceleration was significantly associated with sex, clinical diagnosis, and levels of eight plasma biomarkers, including P-tau217 levels. Additionally, biomarker associations trended more significantly among APOE-ε4 non-carriers. We also identified that methylation levels in CD4 and CD8 T-cell types are associated with age acceleration. DISCUSSION: We demonstrated that biological age acceleration, measured in blood, in a Hispanic cohort enriched for preclinical individuals, can stratify clinical AD risk and is associated with plasma AD biomarker levels. Highlights: Blood-based aging clocks associate with Alzheimer's disease plasma biomarker levels. Biological aging appears relevant to pathological aging in apolipoprotein E (APOE) -ε4 non-carriers. Immune T-cell composition relates to biological aging.