Clinical Factors Associated With Discordant Plasma P-Tau217 and Established Alzheimer Disease Biomarkers

BACKGROUND AND OBJECTIVES: Plasma phosphorylated tau (p-tau) 217 is increasingly used for Alzheimer disease (AD) diagnosis and treatment decisions but may be discordant with established AD biomarkers. False-positive (FP) plasma results may lead to overtreatment and false-negative (FN) results to missed or delayed disease-modifying therapies. We evaluated factors associated with discordant results. METHODS: This retrospective study included participants enrolled in memory and aging studies at Mayo Clinic with "positive" (>0.324 pg/mL) or "negative" (<0.186 pg/mL) plasma p-tau217 results and confirmatory AD biomarkers. Plasma results were classified as true positive (TP), true negative (TN), FP, or FN, referencing amyloid-PET and CSF p-tau181/β-amyloid (Aβ) 42. Clinical and laboratory variables were compared using univariate analyses; multivariable logistic regression evaluated independent associations with discordance. DISCUSSION: Plasma p-tau217 results and established AD biomarkers were discordant in 8.5% of participants. Clinical stage and factors related to brain amyloid clearance, renal clearance, and volume of distribution were associated with discordant results. These insights may inform mechanisms of discordance and identify patients requiring confirmatory biomarker measures.