Comparison of plasma p‐tau217/Aβ42, p‐tau217, and Aβ42/Aβ40 biomarkers by race to detect Alzheimer's disease

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. Inclusion criteria were available plasma, race (people who self-identified as Black/African American [pBlack] or White [pWhite]), cognitive status (normal, mild cognitive impairment [MCI], dementia), and 18F-florbetaben or 18F-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). 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. Plasma p-tau217/Aβ42 had high accuracy to detect AD, with comparable performance across race. We tested plasma phosphorylated tau-217 (p-tau217)/amyloid beta (Aβ)42, 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.