Biomarkers

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.