Plasma biomarkers, brain amyloid pathology, and cortical thickness in a diverse middle-aged community cohort: the HCP-CoBRA study.

INTRODUCTION: We evaluated plasma biomarker association with, and classification accuracies for, Aβ-PET and cortical thickness in the biracial HCP-CoBRA cohort (53% B/AA and 47% NHW). METHODS: In n=218 participants (age 62 [range: 57-71] years, 65% female and 15% Aβ PET-positive), plasma biomarkers (p-tau181, p-tau217, p-tau231, GFAP, NfL, Aβ42/Aβ40) were compared to Aβ-PET and MRI neuroimaging indicators. RESULTS: P-tau217 (Janssen and ALZpath [AUCs=0.915-0.919]) had high sensitivity and specificity (>85%) for Aβ-PET status. All biomarkers except p-tau231 ruled out Aβ-pathology (NPV>95%) but only Janssen p-tau217+ was good for confirmation (PPV=0.909). Plasma biomarkers performed poorly for predicting cortical thickness but were elevated according to joint Aβ-PET-neurodegeneration profiles. Biomarker accuracies for Aβ-PET positivity were unaffected by self-identified race, except ALZpath p-tau217(p=0.024). However, correlations with Aβ-PET varied by self-identified race. DISCUSSION: P-tau217 is a promising tool for Alzheimer's disease-related Aβ pathology in older/middle-aged individuals. However, apparent race-related performances should be further studied.