Demographic and Clinical Characteristics Associated With Serum GFAP Levels in an Ethnically Diverse Cohort

Elevations in circulating glial fibrillary acidic protein (GFAP), a putative marker of reactive astrocytosis, have been found to associate with cognitive decline and dementia status. Further validation in diverse cohorts and evaluation of potential health disparities are necessary for broader generalization. The goal of this study was to examine the associations between demographics, cardiovascular risk factors, and APOE ε4 status with serum GFAP levels among Mexican American and non-Hispanic White older adults across the continuum from cognitively unimpaired to Alzheimer disease dementia. Serum GFAP levels were assayed using a Simoa HD-1 analyzer in older adults enrolled in the observational Texas Alzheimer Research and Care Consortium. Associations between demographic and clinical characteristics with serum GFAP levels were evaluated using linear regression. The diagnostic accuracy of serum GFAP was further examined using area under the receiver operating characteristic curves (AUROC) in univariate and adjusted models, and optimal cut points were derived using the maximum Kolmogorov-Smirnov metric. All models were also stratified by ethnicity and disease stage. A total of 1,156 Mexican American and 587 non-Hispanic White participants were included (mean age = 68 years, standard deviation = 10; 65% female). Older age (β = 0.562 (95% CI 0.515-0.609), < 0.001), apolipoprotein ε4 status (β = 0.139 (95% CI 0.092-0.186), < 0.001), and cognitive impairment (β = 0.150 (95% CI 0.103-0.197), < 0.001) were positively associated with serum GFAP. By contrast, higher body mass index (β = -0.181 (95% CI -0.228 to -0.134), < 0.001), diabetes (β = -0.065 (95% CI -0.112 to -0.018), < 0.001), and tobacco use (β = -0.059 (95% CI -0.106 to -0.012), < 0.001) were inversely associated with serum GFAP. AUROC values were generally comparable across ethnicities and model fit improved with inclusion of additional covariates. However, optimal cut-off values were consistently lower in Mexican Americans relative to non-Hispanic White participants. The study results highlight the importance of understanding the role of broader demographic and clinical factors on circulating GFAP levels within diverse cohorts to enhance precision across clinical, research, and community settings.