# 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.

## Key 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.