Head-to-head comparison of plasma p-tau217 immunoassays for incipient Alzheimer’s disease in community cohorts

Plasma p-tau217 is a promising biomarker for detecting incipient AD pathology, but direct comparison of different p-tau217 assays in community-based cohorts are limited. We evaluated two cohorts from southwestern Pennsylvania, USA; the MYHAT-NI study, which included two-year longitudinal follow-up neuroimaging assessments of Aβ, tau, and cortical thickness; and the Human Connectome Project/CoBRA cohort, targeting a 50:50 split of self-identified Black and non-Hispanic White individuals. Plasma p-tau217 was measured using four different assays: Lumipulse, Johnson & Johnson, ALZpath, and NULISA. Aβ and tau pathologies were assessed with [ 11 C]PiB PET and [ 18 F]Flortaucipir PET, respectively. Clinical Dementia Rating and Montreal Cognitive Assessment were used to assess cognitive performance. We included 344 participants (MYHAT-NI: n = 111, median age 76 [IQR: 72–80], 54% female; HCP/CoBRA: n = 234, median age 62 [IQR: 52–70], 65% female). All four p-tau217 assays exhibited moderate to strong cross-platform correlations (Spearman correlations of 0.40–0.86), and statistically equivalent AUCs (of 0.84–0.90) for determining Aβ positivity. Our findings show strong equivalent performances of plasma p-tau217 assays to identify amyloid positivity across two highly diverse cohorts of community-dwelling older adults.