Characterizing Plasma Biomarkers of Alzheimer's in a Diverse Community-Based Cohort: A Cross-Sectional Study of the HAB-HD Cohort

Background: Due to their low cost, less invasive nature, and ready availability, plasma biomarkers of Alzheimer's disease have been proposed as one-time screening tools for clinical trials and research. The impact of ethnoracial factors on these biomarkers has received little attention. The current cross-sectional study investigated the levels of Aβ₄₀, Aβ₄₂, total tau (t tau), and neurofilament light (NfL) across diagnoses for each of the three major ethnoracial groups in the United States in a community-based cohort of older adults. Methods: A total of 1,862 participants (852 Mexican Americans (MAs); 775 non-Hispanic Whites (NHWs), and 235 African Americans (AAs)) drawn from The Health & Aging Brain Study—Health Disparities (HABS-HD) study were included. Diagnoses were assigned using an algorithm (decision tree) verified by consensus review. Plasma samples were assayed using Simoa technology. Levels of each biomarker were compared for the three ethnoracial groups across cognitive diagnoses using ANOVA covarying sex and age. Results: Significant differences were found across the groups at each level of cognitive impairment. Cognitively unimpaired (CU) AA had significantly lower levels of each of the biomarkers than cognitively unimpaired MA or NHW and NHW had higher levels of Aβ₄₀, and NfL than the other two groups. MA had higher t tau than AA or NHW. Mild cognitive impairment (MCI) group NHW had the highest levels on all the biomarkers and AA had the lowest. NHW and MA have higher levels of Aβ₄₀, Aβ₄₂, and t tau there was no difference between the groups for Aβ₄₂. NHW had significantly higher levels of Aβ₄₀, t tau, and NfL than AA. AA had a higher Aβ₄₂/Aβ₄₀ ratio than either NHW or MA for CU MCI. Conclusions: The use of plasma biomarkers of cognitive decline is promising given their advantages over other biomarkers such as CSF and imaging but as the current research shows, ethnoracial differences must be considered to enhance accuracy and utility. Developing ethnoracial-specific cut points and establishing normative ranges by assay platform for each of the biomarkers are needed. Longitudinal research to assess changes in biomarkers during a cognitive decline is ongoing.