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

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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).

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