Association of Alzheimer's disease genetic risk with age-dependent changes in plasma amyloid-β_42:40 in Veterans

BackgroundIdentifying biomarkers of Alzheimer's disease (AD) is critical for early diagnosis and AD risk assessment.ObjectiveWe 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.MethodsThis 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.ResultsWe 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.ConclusionsThese 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.