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Related Experiment Video

Updated: Jan 7, 2026

Dried Blood Spot Collection of Health Biomarkers to Maximize Participation in Population Studies
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Biomarkers.

Linda K McEvoy1, Bowei Zhang2, Steve Nguyen2

  • 1Kaiser Permanente Washington Health Research Institute, Seattle, WA, USA.

Alzheimer'S & Dementia : the Journal of the Alzheimer'S Association
|December 25, 2025
PubMed
Summary
This summary is machine-generated.

Accelerated epigenetic aging, measured by AgeAccelGrim2, predicts brain atrophy linked to Alzheimer's disease (AD) risk approximately 8 years later in women. This blood-based biomarker also highlights smoking's negative impact on brain health.

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Area of Science:

  • Epigenetics and Aging
  • Neuroscience
  • Alzheimer's Disease Research

Background:

  • Epigenetic age acceleration is linked to adverse health outcomes and mortality.
  • Few studies have prospectively investigated epigenetic age estimators in relation to brain atrophy, particularly in regions vulnerable to Alzheimer's disease (AD).

Purpose of the Study:

  • To examine the association between seven epigenetic age estimators and neuroanatomic risk for AD.
  • To determine if epigenetic age acceleration predicts gray matter atrophy in brain regions vulnerable to AD.

Main Methods:

  • Utilized data from 1196 women in the Women's Health Initiative Memory Study, assessing epigenetic age and AD Pattern Similarity (AD-PS) score, a measure of gray matter atrophy.
  • Employed multiple linear regression, adjusting for various health and demographic factors, to analyze the relationship between epigenetic age estimators and AD-PS score.
  • Evaluated potential effect modification by APOE ε4 status.

Main Results:

  • Two epigenetic age estimators, AgeAccelGrim2 and EEAA, were significantly associated with higher AD-PS scores, indicating greater age acceleration correlated with increased atrophy.
  • The DNA methylation surrogate for smoking pack years within AgeAccelGrim2 was positively associated with AD-PS score.
  • No interaction was found between the identified epigenetic age estimators and APOE ε4 status.

Conclusions:

  • AgeAccelGrim2, a blood-derived epigenetic measure, can predict atrophy in AD-vulnerable brain regions up to 8 years in advance in cognitively healthy women.
  • These findings suggest AgeAccelGrim2 may serve as an early biomarker for AD risk.
  • The study reinforces the detrimental effects of smoking on brain health during aging.