Alzheimer Disease Blood Biomarker Concentrations Across Race and Ethnicity Groups in Middle-Aged Adults.

Importance: The incidence and prevalence of clinical Alzheimer disease (AD) are higher among Black and Latinx older adults than among White older adults. Past studies that compared plasma AD biomarker concentrations among groups minoritized by their race and ethnicity yielded inconsistent findings; however, these efforts did not include population representative samples or statistical procedures to ensure population representation. Objective: To examine race and ethnicity differences in plasma AD biomarker concentrations and in the association between biomarkers and medical conditions in a US population-representative cohort of middle-aged adults (approximately 58 years of age). Design, Setting, and Participants: Data for this cohort study came from the High School and Beyond sample, a nationally representative cohort of high school sophomores and seniors who were recruited in 1980. In 2021, a subset of participants provided blood samples that were assayed for amyloid-β (Aβ42/Aβ40 ratio), phosphorylated tau-181 (pTau-181), neurofilament light chain (NfL), and glial fibrillary acidic protein (GFAP). The analyses for the present study were conducted between July 2, 2024, and August 26, 2025, using data collected during the 2021 follow-up study. Exposures: Race and ethnicity groups and common medical conditions. Main Outcomes and Measures: General linear models with Wald tests were used to compare biomarker concentrations between race and ethnicity groups and to test interactions with common medical conditions using unadjusted biomarker values and models adjusted to ensure population representation with inverse probability weighting and multiple imputation. Results: The sample included 4340 adults (mean [SD; range] age, 58.1 [1.1; 56-63] years; 2400 [55.3%] women); 630 (14.4%) were Black, 900 (20.7%) were Latinx, and 2610 (60.1%) were White. Black participants had a lower Aβ42/Aβ40 ratio (d = -0.002; 95% CI, -0.004 to -0.000; P = .04) and lower NfL concentrations (d = -1.16; 95% CI, -2.15 to -0.16; P = .02) than White participants, but these differences were attenuated when models were adjusted for population representation (d = 0.000; 95% CI, -0.002 to 0.002; P = .85 for Aβ ratio; d = -0.88; 95% CI, -1.78 to 0.02; P = .05 for NfL). Latinx participants had lower GFAP concentrations than White participants (d = -3.87; 95% CI, -7.30 to -0.45; P = .03), but these differences were also attenuated when models were adjusted for population representation (d = 3.36; 95% CI, -3.13 to 9.86; P = .31). In general, estimated biomarker means were similar between race and ethnicity groups. History of type 2 diabetes was associated with increased NfL concentration (d = 0.19; 95% CI, 0.07 to 0.30; P = .04), and high body mass index was associated with lower Aβ42/Aβ40 ratio (d = -0.13; 95% CI, -0.21 to -0.06; P = .02); whereas high cholesterol was associated with lower pTau-181 concentration (d = -0.18; 95% CI, -0.25 to -0.10; P = .01) and high BMI was associated with lower GFAP concentration (d = -0.30; 95% CI -0.44 to -0.16; P = .01). No differences in associations between morbidities and AD biomarker concentrations were detected across race and ethnicity groups. Conclusions and Relevance: In this cohort of middle-aged adults, the use of appropriate statistical estimation to ensure population representation indicated that blood-based AD biomarker concentrations were not distinguishable among race and ethnicity groups. Common medical conditions were associated with plasma biomarker concentrations similarly across race and ethnicity groups. These results highlight the importance of considering population representation and comorbid conditions in AD research to ensure accurate characterization of disease pathophysiology and improve precision of diagnostic and treatment strategies for populations that experience AD disparities.