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

Background: Plasma ptau217 is a promising biomarker for detecting incipient AD pathology, but direct comparison of different ptau217 assays in community-based cohorts are limited. Methods: We evaluated two cohorts from southwestern Pennsylvania, USA; the MYHATNI substudy, which included two-year longitudinal follow-up neuroimaging assessments of Aβ, tau, and cortical thickness; and the Human Connectome Project/CoBRA, 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 [11C]PiB PET and [18F]Flortaucipir PET, respectively. Clinical Dementia Rating (CDR) and Montreal Cognitive Assessment were used to assess cognitive performance. Results: 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 ptau217 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. Conclusions: Our findings showed strong equivalent performances of plasma ptau217 assays to identify amyloid positivity across two highly diverse cohorts of community dwelling older adults.