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

Brodman, S. T.; Heaton, N.; Triana-Baltzer, G.; Zeng, X.; Gogola, A.; Kamboh, M. I.; Villemagne, V. L.; Lopez, O. L.; Kolb, H.; Deek, R. A.; Cohen, A. D. D.; Karikari, T. K.

2025-07-11 neurology
10.1101/2025.07.10.25331312 medRxiv
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INTRODUCTIONWe evaluated plasma biomarker association with, and classification accuracies for, A{beta}-PET and cortical thickness in the biracial HCP-CoBRA cohort (53% B/AA and 47% NHW). METHODSIn n=218 participants (age 62 [range: 57-71] years, 65% female and 15% A{beta} PET-positive), plasma biomarkers (p-tau181, p-tau217, p-tau231, GFAP, NfL, A{beta}42/A{beta}40) were compared to A{beta}-PET and MRI neuroimaging indicators. RESULTSP-tau217 (Janssen and ALZpath [AUCs=0.915-0.919]) had high sensitivity and specificity (>85%) for A{beta}-PET status. All biomarkers except p-tau231 ruled out A{beta}-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 A{beta}-PET-neurodegeneration profiles. Biomarker accuracies for A{beta}-PET positivity were unaffected by self-identified race, except ALZpath p-tau217(p=0.024). However, correlations with A{beta}-PET varied by self-identified race. DISCUSSIONP-tau217 is a promising tool for Alzheimers disease-related A{beta} pathology in older/middle-aged individuals. However, apparent race-related performances should be further studied.

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