Age-related breakpoints identified for plasma Aβ42/40 and p-tau181, informing Alzheimer's disease risk across aging

Understanding the precise timing when Alzheimer's disease (AD) biomarkers become informative is crucial for early detection and intervention. Current diagnostic approaches often rely on established thresholds, but these may not fully capture the dynamic, age-related changes in biomarker trajectories. Identifying specific age-related 'breakpoints'—points where biomarker trajectories significantly change slope—could offer a more nuanced understanding of AD progression. This approach helps pinpoint when neuropathological changes begin to accelerate, providing a critical window for potential therapeutic strategies before widespread cognitive decline.

Researchers analyzed data from 2082 participants in the Mayo Clinic Study of Aging to identify age-related breakpoints in plasma amyloid beta (Aβ)42/40 and phosphorylated tau (p-tau)181. They employed statistical models to detect slope-changing trajectories for these key AD biomarkers across the aging spectrum. The study also examined associations with global cognition and fluency, and explored potential effect modification by demographic factors such as sex, race, and APOE ∈4 genotype. This design aimed to determine when these biomarkers become most predictive and how their trajectories evolve with age.

The study successfully identified age-related breakpoints for both plasma Aβ42/40 and p-tau181, indicating specific ages when the trajectories of these Alzheimer's disease biomarkers undergo significant changes. These breakpoints suggest that the informativeness of these biomarkers shifts across the aging spectrum, providing insights into the dynamic nature of AD neuropathology. Importantly, the analysis revealed no significant association between these biomarkers and measures of global cognition or fluency in the studied population. This suggests that while biomarker changes are occurring, they may not immediately translate into measurable cognitive deficits across all individuals or at all stages. > Some effect modification was observed, with stronger associations between biomarkers and outcomes in women, Black participants, and individuals carrying the APOE ∈4 allele, highlighting potential demographic and genetic influences on biomarker-cognition relationships.