Association of Plasma Biomarkers of Alzheimer Disease With Cognition and Medical Comorbidities in a Biracial Cohort

Background and objectives: Recent advances in blood-based biomarkers offer the potential to revolutionize the diagnosis and management of Alzheimer disease (AD), but additional research in diverse populations is critical. We assessed the profiles of blood-based AD biomarkers and their relationships to cognition and common medical comorbidities in a biracial cohort.

Methods: Participants were evaluated through the Mayo Clinic Jacksonville Alzheimer Disease Research Center and matched on age, sex, and cognitive status. Plasma AD biomarkers (β-amyloid peptide 1-42 [Aβ_42/40], plasma tau phosphorylated at position 181 [p-tau₁₈₁], glial fibrillary acidic protein [GFAP], and neurofilament light) were measured using the Quanterix SiMoA HD-X analyzer. Cognition was assessed with the Mini-Mental State Examination. Wilcoxon rank sum tests were used to assess for differences in plasma biomarker levels by sex. Linear models tested for associations of self-reported race, chronic kidney disease (CKD), and vascular risk factors with plasma AD biomarker levels. Additional models assessed for interactions between race and plasma biomarkers in predicting cognition.

Results: The sample comprised African American (AA; N = 267) and non-Hispanic White (NHW; N = 268) participants, including 69% female participants and age range 43-100 (median 80.2) years. Education was higher in NHW participants (median 16 vs 12 years, p < 0.001) while APOE ε4 positivity was higher in AA participants (43% vs 34%; p = 0.04). We observed no differences in plasma AD biomarker levels between AA and NHW participants. These results were unchanged after stratifying by cognitive status (unimpaired vs impaired). Although the p-tau₁₈₁-cognition association seemed stronger in NHW participants while the Aβ_42/40-cognition association seemed stronger in AA participants, these findings did not survive after excluding individuals with CKD. Female participants displayed higher GFAP (177.5 pg/mL vs 157.73 pg/mL; p = 0.002) and lower p-tau₁₈₁ (2.62 pg/mL vs 3.28 pg/mL; p = 0.001) levels than male participants. Diabetes was inversely associated with GFAP levels (β = -0.01; p < 0.001).

Discussion: In a biracial community-based sample of adults, we observed that sex differences, CKD, and vascular risk factors, but not self-reported race, contributed to variation in plasma AD biomarkers. Although some prior studies have reported primary effects of race/ethnicity, our results reinforce the need to account for broad-based medical and social determinants of health (including sex, systemic comorbidities, and other factors) in effectively and equitably deploying plasma AD biomarkers in the general population.