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Basic Science and Pathogenesis.

Jaclyn M Eissman1,2, Min N Qiao1,2, Vrinda Kalia3

  • 1The Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University, New York, NY, USA.

Alzheimer'S & Dementia : the Journal of the Alzheimer'S Association
|December 24, 2025
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Summary
This summary is machine-generated.

Biological age, measured by epigenetic clocks, predicts Alzheimer's disease (AD) pathology. This finding aids in stratifying AD risk, especially in early stages, by identifying key plasma biomarkers.

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Area of Science:

  • Gerontology
  • Neuroscience
  • Epigenetics

Background:

  • Advancing chronological age is a primary risk factor for Alzheimer's disease (AD).
  • Individual aging trajectories vary, necessitating novel biomarkers for risk stratification, particularly in preclinical AD.
  • Epigenetic clocks, assessing biological age via DNA methylation, offer a potential tool for this stratification.

Purpose of the Study:

  • To compute epigenetic clocks (biological age) and assess their association with dementia and AD biomarkers.
  • To investigate the correlation between biological age and chronological age, and with sex.
  • To validate these correlations in independent cohorts and brain tissue.

Main Methods:

  • Utilized whole blood and brain DNA methylation data from the EFIGA cohort (N=731).
  • Computed Horvath and Hannum epigenetic clocks and calculated age acceleration.
  • Employed linear regression models to test associations between biological age/age acceleration and plasma dementia/AD biomarkers, adjusting for multiple comparisons (FDR).

Main Results:

  • Biological age significantly correlated with chronological age and sex in both blood and brain data.
  • Replicated correlations in an independent cohort (ROS/MAP).
  • Seven plasma biomarkers, including p-tau217, p-tau181, GFAP, p-tau231, NfL, Aβ40, and total-tau, were significantly associated with biological age.

Conclusions:

  • Biological age is a significant predictor of Alzheimer's disease pathology across preclinical and clinical stages.
  • Future research will evaluate age acceleration as a pathology predictor and validate biomarker associations with autopsy-confirmed neuropathology.
  • Investigating sex and APOE-ε4 carrier status stratification will further elucidate AD biomarker relationships.