# Exploring Racial Differences in the Association of Plasma Biomarkers and APOE4 Genotype in a Large Memory Clinic Cohort

## TL;DR

This study finds that race influences how APOE4 genotype relates to Alzheimer's biomarkers and cognitive decline in a memory clinic cohort.

## Contribution

The study reveals racial differences in APOE4's impact on plasma biomarkers and cognitive stability.

## Key findings

- Black/African American APOE4 non-carriers showed the most stable cognition over time.
- Non-Hispanic White individuals experienced more cognitive decline than Black/African American individuals regardless of APOE4 status.
- The APOE4 effect on BD-tau was insignificant in Black/African American individuals, but p-tau217 had a larger effect in this group.

## Abstract

The APOE4 is a major genetic risk factor for Alzheimer's disease (AD) and has been shown to impact plasma AD biomarker levels. We utilized a large memory clinic cohort to assess potential differences in this association race.

Participants at the University of Pittsburgh Alzheimer's Disease Research Center (Pitt‐ADRC) underwent baseline blood collection and cognitive function assessment using the Clinical Dementia Rating (CDR) scale, followed by annual CDR assessments for a median of 3.0 year (IQR 1.9‐5.9). APOE genotyping was determined using TaqMan assays. Plasma p‐tau181, p‐tau217, brain‐derived tau (BD‐tau), GFAP and NfL, were measured using SIMOA assays. Cohen's d and Kaplan‐Meier analysis were employed for statistical inference.

This study included 4,073 participants (59.9% female; 90.2% self‐identified non‐Hispanic White [NHW]), aged 71.9 ± 9.8 years. Both APOE4 genotype and race were significantly associated with cognitive decline. Black/African American (B/AA) APOE4 non‐carriers had the most stable cognition over time, with a median stability of 11.3 years, followed by 7.2 years for B/AA carriers. Importantly, NHW showed more cognitive decline than B/AA regardless of APOE4 carriage, with median stability times of 4.9 and 6.0 years for APOE4 carriers and non‐carriers, respectively. All biomarkers, except NfL, showed significant APOE4‐dependent levels, with effect sizes (carriers/non‐carriers) of 0.176 for p‐tau181, 0.361 for p‐tau217, 0.118 for BD‐tau, and 0.215 for GFAP. The APOE4 effect on BD‐tau was insignificant in B/AA, but p‐tau217 had a larger effect size in B/AA (0.50) than NHW (0.35). The p‐tau217/BD‐tau ratio further highlighted differences between racial groups, with effect sizes of 0.39 for B/AA and 0.07 for NHW.

Racial identity may significantly influence the associations between APOE4 genotype and plasma biomarkers. This should be considered when applying these biomarkers in diverse populations.