Change in Alzheimer’s Disease Blood-Based Biomarkers and Associations With Cortical Thickness

TL;DR

This study explores how blood-based biomarkers for Alzheimer’s disease relate to brain changes in older adults, finding that certain biomarkers are linked to thinner brain cortex.

Contribution

The study identifies longitudinal changes in blood biomarkers like p-Tau181, NfL, and GFAP as predictors of late-life cortical thinning.

Findings

Higher midlife p-Tau181 and increases in NfL and GFAP from midlife to late-life are associated with lower late-life cortical thickness.

Concurrent p-Tau181, NfL, and GFAP levels are linked to reduced cortical thickness, especially in those aged 75 and older.

Longitudinal research is needed to determine if these biomarkers predict future brain atrophy.

Abstract

Blood-based biomarkers show promise as a noninvasive method for measuring Alzheimer’s disease pathology and neurodegeneration throughout the lifecourse. However, the relationship between longitudinal changes in these biomarkers and late-life brain morphology in community-dwelling populations requires further investigation. Between 2011 and 2013, 1,977 participants from the Atherosclerosis Risk in Communities Study received underwent 3 Tesla magnetic resonance imaging scans. Whole-brain cortical thickness was quantified by Freesurfer. Stored plasma samples collected in midlife (1993-95, mean age 59.0 years) and late-life (2011-13, mean age 76.8 years) from a subsample of 1,515 participants (60.7% female, 25.5% Black adults) were assayed in 2022 using Quanterix SiMoA. The assay quantified amyloid-β (Aβ)42/40, phosphorylated tau at threonine 181 (p-Tau181), neurofilament light (NfL), and glial fibrillary acidic protein (GFAP). Linear regression models estimated the association of blood-based biomarkers from midlife, late-life, and the change from midlife to late-life with cortical thickness in late-life. In models adjusted for demographics, lifestyle factors, cardiovascular factors, and the presence of APOE ε4 alleles, higher midlife measures of p-Tau181 and increases from midlife to late-life in NfL and GFAP were associated with lower cortical thickness in late-life. Concurrent measures of p-Tau181, NfL, and GFAP were associated with lower cortical thickness in late-life and exhibited a stronger association among participants ≥75 years old compared to participants <75 years old. Additional longitudinal research is needed to determine whether blood-based biomarkers predict cortical thinning over time and may serve as an early indicator of accelerated brain atrophy.