Plasma biomarkers, brain amyloid‐beta pathology, and cortical thickness in a non‐Hispanic White and Black/African American middle‐aged community cohort: The HCP‐CoBRA study

INTRODUCTION We evaluated plasma biomarker association with, and classification accuracies for, amyloid beta–positron emission tomography (Aβ‐PET) and cortical thickness in the biracial Human Connectome Project–Connectomics in Brain Aging (HCP‐CoBRA) cohort (53% Black/African American [B/AA] and 47% non‐Hispanic White [NHW]). METHODS In n = 218 participants (median age 62, range: 57–71] years, 65% female and 15% Aβ‐PET positive), plasma biomarkers (phosphorylated tau‐181 [p‐tau181], p‐tau217, p‐tau231, glial fibrillary acidic protein [GFAP], neurofilament light chain [NfL], and Aβ42/Aβ40) were compared to Aβ‐PET and magnetic resonance imaging (MRI) neuroimaging indicators. RESULTS Plasma p‐tau217 (Johnson & Johnson and ALZpath [areas under the curve [AUCs] = 0.915 vs. 0.919]) had high sensitivity and specificity (>85%) for Aβ‐PET status. All plasma biomarkers except p‐tau231 effectively ruled out Aβ pathology (negative predictive value [NPV] >95%) but only Johnson & Johnson p‐tau217+ was good for confirmation (covariate‐adjusted positive predictive value [PPV] = 0.909). The plasma biomarkers performed poorly for identifying cortical thickness status but were elevated according to joint Aβ‐PET and neurodegeneration profiles. Plasma biomarker accuracies for Aβ‐PET positivity were unaffected by self‐identified race, except for ALZpath p‐tau217 ( p = 0.024). However, correlations with Aβ‐PET standardized uptake value ratio varied by self‐identified race. DISCUSSION Plasma p‐tau217 is a promising tool for Alzheimer's disease–associated Aβ pathology in older/middle‐aged individuals. However, apparent race‐related performances should be further studied. Highlights Plasma phosphorylated tau‐217 (p‐tau217) and glial fibrillary acidic protein (GFAP) best predicted abnormal brain amyloid beta–positron emission tomography (Aβ‐PET). Plasma p‐tau217 accurately identified abnormal Aβ‐PET (Johnson & Johnson p‐tau217: area under the curve [AUC] = 0.9145, 95% confidence interval [CI] = 0.8367–0.9923; ALZpath p ‐tau217: AUC = 0.9198, 95% CI = 0.8585–0.981) followed by GFAP and Aβ42/40 ratio (GFAP: AUC = 0.8529, 95% CI = 0.7485–0.9573; Aβ42/40:AUC = 0.7962, 95% CI = 0.6581–0.9346). All plasma biomarkers performed poorly in identifying cortical thickness, despite being higher according to combined Aβ‐PET and neurodegeneration profiles. Correlations of p‐tau217 (Johnson & Johnson p < 0.001), p‐tau181 ( p = 0.005), and Aβ42/40 ( p = 0.004) with Aβ‐PET in predicting amyloid burden were stronger in self‐identified non‐Hispanic Whites vs Black/African Americans. Biomarker accuracies for Aβ‐PET positivity were unaffected by self‐identified race, except ALZpath p‐tau217 ( p = 0.024).