Age-Related Prevalence of Abnormal Plasma p-Tau217 Across Racial Ethnic Groups in the Health and Aging Brain Study-Health Disparities

Background and ObjectivesPlasma phosphorylated tau at threonine 217 (p-Tau217) has demonstrated high diagnostic accuracy for Alzheimer disease (AD), yet most validation studies have been conducted in predominantly non-Hispanic White (NHW) cohorts. Whether established abnormality thresholds generalize across racially and ethnically diverse populations remains unclear. We examined age-related prevalence of abnormal plasma p-Tau217 using a PET-anchored cutoff across NHW, non-Hispanic Black (NHB), and Hispanic participants in a community-based cohort and evaluated the influence of APOE ε4 and cardiometabolic risk factors on p-Tau217 and its association with clinical cognitive impairment. MethodsWe conducted a cross-sectional analysis of baseline data from the Health and Aging Brain Study-Health Disparities, a community-based cohort. Participants underwent standardized clinical evaluation and blood biomarker assessment. Plasma p-Tau217 was measured using the Simoa HD-X platform and dichotomized as abnormal (>0.42 pg/mL) based on PET-validated thresholds. Multivariable logistic regression evaluated associations with abnormal p-Tau217, adjusting for demographics, estimated glomerular filtration rate, APOE ε4 status, and cardiometabolic conditions. Analyses were stratified by race and ethnicity and cognitive status. ResultsAmong 2,798 participants (mean age 65.3 ± 8.7 years; 62% female), abnormal plasma p-Tau217 was most frequent in NHW participants (40%), followed by NHB (25%) and Hispanic (22%) participants. Clinical cognitive impairment was more common among NHB (41%) and Hispanic (28%) than NHW (17%) participants. Older age was associated with greater odds of abnormal p-Tau217 (odds ratio [OR] 1.08 per year, 95% CI 1.07–1.09), as was APOE ε4 carrier status (OR 3.32, 95% CI 2.65–4.17). Lower eGFR was independently associated with abnormal p-Tau217 (OR 0.97 per unit, 95% CI 0.96–0.97). After adjustment, NHB participants had lower odds of abnormal p-Tau217 than NHW participants (OR 0.61, 95% CI 0.45–0.82), while the association for Hispanic participants was attenuated (OR 0.76, 95% CI 0.56–1.03). Abnormal p-Tau217 was associated with higher odds of clinical cognitive impairment (OR 2.19, 95% CI 1.74–2.76). DiscussionPlasma p-Tau217 increased with age and APOE ε4 across racial and ethnic groups; however, abnormal p-Tau217 was less prevalent among NHB and Hispanic participants despite higher rates of cognitive impairment. The cross-sectional design and use of a threshold derived primarily in NHW cohorts limit causal inference and highlight the need for longitudinal validation in diverse populations.