Comparison of plasma p‐tau217/Aβ42, p‐tau217, and Aβ42/Aβ40 biomarkers by race to detect Alzheimer's disease
Katheryn A Q Cousins, Magdalena Korecka, Yang Wan, Amberley Vulaj, Christopher D. Brown, Thomas F. Tropea, Edward B. Lee, Duygu Tosun, Susan Landau, Ozioma C. Okonkwo, Mónica Rivera Mindt, Michael W. Weiner, David J. Irwin, David A. Wolk, Leslie M. Shaw, and the Alzheimer's Disease Neuroimaging Initiative
Abstract
INTRODUCTION: In clinically and racially diverse training and test sets, we evaluated and validated Alzheimer's disease (AD) plasma biomarkers: phosphorylated tau-217 (p-tau217), amyloid beta 1-42/1-40 (Aβ42/Aβ40), and p-tau217/Aβ42. METHODS: F-florbetapir positron emission tomography (PET) data. In the training set (n = 289; 28% pBlack), we used receiver-operating characteristic (ROC) analysis to calculate two cut points (0.95 sensitivity and specificity) to detect amyloid PET positivity. Cut points were validated in an independent test set (n = 846; 12% pBlack). RESULTS: In the test set, plasma p-tau217/Aβ42 had the highest accuracy (pBlack: 0.88, pWhite: 0.91) and lowest proportion of intermediate classifications (≤0.16), with no classification difference by race (odds ratio [OR] = 1.45, 95% confidence interval [CI] = 0.66-2.95, p = 0.33). False negatives were more likely to be cognitively normal (vs mild cognitive impairment [MCI]; OR = 7.79, 95% CI = 2.33-40.81, p = 5.1e-05) than correct classifications. DISCUSSION: Plasma p-tau217/Aβ42 had high accuracy to detect AD, with comparable performance across race. HIGHLIGHTS: , p-tau217, and Aβ42/Aβ40 in diverse training and test sets. In models, race × amyloid PET interactions were not significant. Plasma p-tau217/Aβ42 had the highest accuracy in people who self-identified as Black/African American (pBlack; 0.88) and people who self-identified as White (pWhite; 0.91). Plasma p-tau217/Aβ42 had the lowest proportion of intermediate cases (range = 0.09-0.16). False negatives were more likely to have normal cognition, female sex, and high body mass index.