Biological Age and Age Acceleration Predict Alzheimer's Disease Plasma Biomarker Levels

Epigenetic clocks can predict pathological aging associated with Alzheimer's disease (AD) risk, albeit findings are mixed regarding if clocks are predictive in blood and in non-European populations. We constructed epigenetic clocks from blood methylation data in 704 older Hispanic adults and tested the association with a clinical diagnosis of AD and plasma biomarker levels. Biological age and age acceleration, the rate of biological aging, were significantly associated with sex, clinical diagnosis, and levels of eight plasma biomarkers, including P-Tau217 levels. Additionally, biomarker associations trended more significant among APOE-ε4 non-carriers. We also identified that methylation levels in CD4 and CD8 T-cell types are associated with biological aging and showed slightly stronger associations in men. We demonstrate that biological aging, in blood, in a Hispanic cohort of both demented and non-demented individuals, can stratify AD risk, predicting plasma biomarker levels even in preclinical disease.