Yoav D Piura, Paula A Aduen, Leah Schecter, Manoj K Jain, Alicia Algeciras-Schimnich, Daniel J Figdore, Joshua Bornhorst, Ronald C Petersen, Clifford R Jack Jr, Neill R Graff-Radford, Christian Lachner, Gregory S Day
Among 191 participants (57 Black, 46 Hispanic White, 88 non-Hispanic White), age-adjusted plasma p-tau217 and p-tau217/Aβ42 performed similarly in detecting amyloid-positive individuals (≥ 25 Centiloids), regardless of race/ethnicity. Both measures independently correlated with amyloid deposition, whereas estimated glomerular filtration rate (eGFR) correlated solely with p-tau217. Pre-clinical AD optimized cutoffs (p-tau217 ≥ 0.132 pg/ml; p-tau217/Aβ42 ≥ 0.0059) outperformed cutoffs established in symptomatic individuals (sensitivity: 83% vs. 57%; 77% vs. 63%; negative predictive value [NPV] > 93%).
INTRODUCTION: Plasma p-tau217 and p-tau217/Aβ42 reliably identify non-Hispanic White individuals with symptomatic and pre-clinical AD. However, performance across ethnoracially diverse groups remains unknown.
METHODS: Cognitively normal Black, Hispanic, and non-Hispanic White participants completed cognitive evaluations, brain magnetic resonance imaging (MRI), amyloid and tau positron emission tomography (PET), and measures of kidney function. Plasma p-tau217 and Aβ42 were measured using Fujirebio Lumipulse assays. Pre-clinical AD detection was evaluated using symptomatic and cohort-derived optimized cutoffs.
RESULTS: Among 191 participants (57 Black, 46 Hispanic White, 88 non-Hispanic White), age-adjusted plasma p-tau217 and p-tau217/Aβ42 performed similarly in detecting amyloid-positive individuals (≥ 25 Centiloids), regardless of race/ethnicity. Both measures independently correlated with amyloid deposition, whereas estimated glomerular filtration rate (eGFR) correlated solely with p-tau217. Pre-clinical AD optimized cutoffs (p-tau217 ≥ 0.132 pg/ml; p-tau217/Aβ42 ≥ 0.0059) outperformed cutoffs established in symptomatic individuals (sensitivity: 83% vs. 57%; 77% vs. 63%; negative predictive value [NPV] > 93%).
DISCUSSION: Plasma biomarkers performed similarly across ethnoracially diverse cohorts. Optimized cutoffs may improve early detection and trial enrollment.