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

Age acceleration was significantly associated with clinical AD diagnosis in older Hispanic adults.

• Study population comprised 704 older Hispanic adults with blood methylation data.
• The cohort was enriched for preclinical individuals.
• Biological age and age acceleration were calculated from blood methylation data.
• Age acceleration was significantly associated with sex and clinical diagnosis.

Age acceleration was significantly associated with levels of eight plasma AD biomarkers, including P-tau217.

• Eight plasma biomarkers showed significant associations with age acceleration.
• P-tau217 levels were specifically identified as significantly associated with age acceleration.
• Biomarker associations trended more significantly among APOE-ε4 non-carriers.
• Biomarkers were measured as antemortem plasma levels.

Associations between age acceleration and AD biomarkers trended more significantly among APOE-ε4 non-carriers.

• APOE-ε4 carrier status modulated the relationship between biological age acceleration and plasma biomarker levels.
• Biomarker associations trended more significantly among APOE-ε4 non-carriers compared to carriers.
• This suggests biological aging may be particularly relevant to pathological aging in APOE-ε4 non-carriers.

Methylation levels in CD4 and CD8 T-cell types are associated with age acceleration.

• Cell-type-specific methylation analysis identified immune T-cell composition as related to biological aging.
• Both CD4 and CD8 T-cell types showed associations with age acceleration.
• This finding implicates immune T-cell composition in the biology of age acceleration measured in blood.

Epigenetic clocks calculated from blood methylation data can stratify clinical AD risk in a Hispanic population.

• The study was conducted in 704 older Hispanic adults, a non-European population.
• Prior findings on whether epigenetic clocks associate with blood-based biomarkers and in non-European populations have been mixed.
• Biological age acceleration measured in blood successfully stratified clinical AD risk in this Hispanic cohort.
• Blood-based aging clocks were shown to associate with Alzheimer's disease plasma biomarker levels.