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

Abstract

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.

Figure. Profiles of Plasma Biomarkers of Alzheimer Disease by Sex and Self-Reported Race

Analyses were performed on a biracial sample matched on age, sex, and clinical diagnosis. Box plots display the distributions of plasma biomarker (Aβ_42/40, GFAP, NfL, and p-tau₁₈₁) levels among female vs male participants (A) and among AA vs NHW participants (B). Female participants displayed higher GFAP and lower p-tau₁₈₁ levels than male participants, differences that persisted after excluding individuals with CKD. No differences by self-reported race were observed for any plasma biomarker. AA = African American; Aβ = β-amyloid; Aβ₄₀ = Aβ peptide 1–40; Aβ₄₂ = Aβ peptide 1–42; CKD = chronic kidney disease; GFAP = glial fibrillary acidic protein; NfL = neurofilament light; NHW = non-Hispanic White; p-tau₁₈₁ = plasma tau phosphorylated at position 181.