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

Abstract Background To guide blood biomarker implementation to detect Alzheimer’s disease (AD), evaluations in clinically and racially diverse samples are needed. Here, we compare plasma biomarkers phosphorylated tau 217 (p‐tau 217 ), β‐amyloid (Aβ) 1‐42/1‐40 (Aβ 42 /Aβ 40 ) ratio, and p‐tau 217 /Aβ 42 ratio in a University of Pennsylvania (UPenn) sample that includes self‐identified White and Black/African American individuals with and without cognitive impairment, and independently validate findings in the first 100 AD Neuroimaging Initiative (ADNI) autopsy participants. Methods UPenn inclusion criteria were plasma p‐tau 217 , Aβ 42 , and Aβ 40 (n = 213) assayed using the automated Fujirebio platform, self‐reported race (156 White [including 1 Hispanic White, 2 multiracial] and 57 Black), and 18 F‐florbetaben PET scan to determine Aβ positivity by visual read (87 Aβ+, 126 Aβ‐). Participants were cognitively Normal (n = 128) or Impaired (n = 85) according to National Alzheimer’s Coordinating Center (NACC) Uniform Dataset 3.0 criteria. Linear models tested if plasma biomarkers (dependent variable, log‐transformed) differed by race and/or Aβ PET status (±). To confirm observed racial differences, linear models tested the interaction of race by global Aβ PET standardized uptake value ratio (SUVR). Models covaried for age at plasma, sex, 2021 national area deprivation index (ADI), and APOE ε4. Receiver operating characteristic (ROC) with bootstrapping (2000 iterations) compared biomarker performance (area under the curve [AUC]) and calculated 2 thresholds at 0.95 sensitivity and 0.95 specificity. Plasma p‐tau 217 cutpoints were validated in ADNI autopsy sample (n = 100); high/intermediate AD neuropathologic change considered AD+. Results P‐tau 217 /Aβ 42 had the highest performance to discriminate Aβ+ from Aβ‐ (Table 1A,1B; all AUC≥0.90), and p‐tau 217 showed excellent accuracy in ADNI sample (0.96; Table 1B). Linear models showed that Black individuals had significantly higher Aβ 42 (β = 0.098, p = 0.0014); no difference was observed for p‐tau 217 or p‐tau 217 /Aβ 42 (both p ≥0.43) (Figure 1). A Race X Aβ PET SUVR interaction confirmed this difference for plasma Aβ 42 (β = ‐0.44, p = 0.00051; Figure 2). Conclusion Findings indicate plasma p‐tau 217 levels do not differ by race, while plasma Aβ 42 /Aβ 40 was higher in Black individuals even after accounting for differences in Aβ PET SUVR and ADI. Future work will test biomarkers in a larger sample, and examine the influence of comorbidities on differences in plasma levels and accuracy.