Generalizability of blood-based biomarkers of Alzheimer's disease and related dementias in a multicultural cohort of older adults: The effect of adjustment for kidney function

Background Interpreting blood-based biomarkers of Alzheimer's disease and related dementias (ADRD) in a multicultural cohort is complicated by inconsistent evidence on racial differences. Kidney function, which varies by race and influences biomarker levels, is often overlooked, potentially contributing to these inconsistencies. Objective To characterize racial differences in plasma levels of ADRD biomarkers after adjusting for comorbidities and assessed the impact of estimated glomerular filtration rate (eGFR) adjustment using either race-specific or race-neutral equations. Methods Data from the Einstein Aging Study, a multicultural cohort of older adults, included plasma biomarkers (Aβ40, Aβ42, pTau181, NfL, GFAP). Linear regression models evaluated racial differences in AD plasma biomarkers, adjusting for age, sex, body mass index, kidney function assessed via race-adjusted (eGFR-ASR) and race-neutral (eGFR-AS) equations, comorbidities (e.g., diabetes, hypertension, cardiovascular disease), and APOE ε4 carrier status. Results Among 269 participants, Black participants had lower plasma levels of Aβ40 (p = 0.004), Aβ42 (p = 0.002), and NfL (p = 0.022) compared to White participants. We observed modest variation in the magnitude of racial differences depending on the method used to adjust for kidney function. However, race differences remained after adjusting for comorbidities or APOE ε4 carrier status. Conclusions Observed racial differences in ADRD biomarkers remain unexplained by kidney function, comorbidities or APOE ε4 carrier status. Future research focusing on associations between blood-based biomarkers and gold standards of brain pathology in multicultural cohorts are essential to advance the usability of blood biomarkers.