Evaluation of plasma p-tau217 for detecting amyloid pathology in a diverse and heterogeneous community-based cohort
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INTRODUCTION
Studies suggest excellent performance of plasma p-tau217 for detecting amyloid pathology, though studies in more diverse populations are needed to validate previously determined cutpoints.
METHODS
Plasma p-tau217 utility for detecting amyloid pathology (Aβ) via amyloid PET ( n =598) and/or cerebrospinal fluid (CSF; n =154) was assessed in a heterogeneous, community-based cohort in the Wake Forest Alzheimer’s Disease Research Center (WFADRC). Participants ( 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% with 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: AUC: 94%-97%, cutpoint≥.338 pg/mL; CSF: AUC = .84, cutpoint ≥.307 pg/mL).
DISCUSSION
Plasma p-tau217 is an accurate indicator of amyloid pathology in a heterogeneous cohort, and superior to other plasma biomarkers assessed. Longitudinal analyses assessing impact of comorbidities on p-tau217 utility for disease progression are underway.
HIGHLIGHTS
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The WFADRC is a diverse and heterogeneous cohort.
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P-tau217 levels were lower, on average, in cognitively unimpaired participants, females, and Black participants.
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Plasma p-tau217 classified amyloid PET positive individuals with high precision and performed better than p-tau181.
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Cutpoints and reference ranges of plasma p-tau217 were lower compared to recently published thresholds.
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Combining cutpoint approaches, a 4-tier system captured cohort heterogeneity.
