Evaluation of plasma p-tau217 for detecting amyloid pathology in a heterogeneous community-based cohort

Abstract

INTRODUCTION: Studies suggest excellent performance of plasma phosphorylated tau 217 (p-tau217) for detecting amyloid pathology, though studies in more representative populations are needed to validate previously determined cutpoints. METHODS: Plasma p-tau217 utility for detecting amyloid pathology (Aβ) via amyloid positron emission tomography (PET) was assessed in a heterogeneous, community-based cohort in the Wake Forest Alzheimer's Disease Research Center (WFADRC). Participants with baseline plasma data (n = 598) were 21% Black; 313 cognitive unimpaired (CU), 214 mild cognitive impairment (MCI), and 64 dementia (DEM); 49% prediabetic, 44% hypertensive, 29% overweight/obese; and 64% had mild-to-moderate kidney disease. Gaussian-mixture models, logistic regression, and receiver operating curve analyses were performed. RESULTS: Plasma p-tau217 was associated with elevated Aβ deposition and accurately classified Aβ-positive participants (PET [n = 307]: area under the curve [AUC] = 94%–97%, cutpoint ≥ 0.338 pg/mL). DISCUSSION: Plasma p-tau217 is an accurate indicator of amyloid pathology in a heterogeneous cohort and is superior to other plasma biomarkers assessed. Highlights: The Wake Forest Alzheimer's Disease Research Center (WFADRC) is a heterogeneous cohort. p-tau217 levels were lower, on average, in cognitively unimpaired participants, females, and Black participants. Plasma p-tau217 classified amyloid positron emission tomography (PET)-positive individuals with high precision and performed better than p-tau181. Cutpoints and reference ranges of plasma p-tau217 were lower compared to recently published thresholds. Combining cutpoint approaches, a four-tier system captured cohort heterogeneity.