Association of Alzheimer's disease genetic risk with age-dependent changes in plasma amyloid-β 42:40 in Veterans

Abstract

Background

Identifying biomarkers of Alzheimer's disease (AD) is critical for early diagnosis and AD risk assessment.

Objective

We examined the hypothesis that the plasma amyloid-β 42 and 40 (Aβ_42:40) ratio has a curvilinear relationship with age among individuals who are at higher genetic risk for AD.

Methods

This study investigated the relationship between plasma amyloid-β 42 and 40 (Aβ_42:40) ratio and age in 315 men and women Veterans, including those at genetic risk for AD. Hierarchical regression models investigated linear and nonlinear relationships between age, genetic risk, and Aβ_42:40.

Results

We observed a curvilinear relationship between age and Aβ_42:40 in individuals with higher genetic risk, characterized by an increase in the Aβ_42:40 during midlife followed by a decrease in older age.

Conclusions

These findings highlight distinct patterns in Aβ metabolism among genetically predisposed individuals, suggesting that early metabolic shifts may play a role in the progression of AD. Understanding these nuanced changes is essential for refining the use of Aβ_42:40 ratio as a biomarker, potentially leading to more accurate risk stratification and earlier intervention strategies in AD.

Keywords

Alzheimer's disease amyloid-β biomarkers genetic risk score Veterans

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