Abstract
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" (Results
Among 706 participants (median 70.0 [interquartile range 15.8] years; 54% male), 60 (8.5%) had discordant plasma p-tau217 results. FN results (5.6%) were more frequent than FP results (2.8%; p = 0.007). Discordance was associated with older age (odds ratio [OR] 1.61 per decade, 95% CI 1.23-2.14) and obstructive sleep apnea (OR 1.94, 95% CI 1.08-3.49). FN (vs TP) results were associated with milder clinical stage (global Clinical Dementia Rating [CDR] ≤0.5 vs CDR ≥1; p 2, 95% CI 1.03-1.20), and higher estimated glomerular filtration rate (eGFR: OR 1.33/10 mL/min/1.73 m2, 95% CI 1.05-1.69). In age-adjusted models, body mass index (OR 1.14, 95% CI 1.03-1.25), eGFR (OR 1.63/10 mL/min/1.73 m2, 95% CI 1.22-2.16), and earlier clinical stage (CDR ≤0.5) were independently associated with FN results. FP (vs TN) results were associated with older age (OR 2.37, 95% CI 1.36-4.09), thyroid disease (OR 4.41, 95% CI 1.36-14.3), lower eGFR (OR 0.48/10 mL/min/1.73 m2, 95% CI 0.31-0.66), and advanced disease stage (CDR ≥1). In age-adjusted models, eGFR (OR 0.54/10 mL/min/1.73 m2, 95% CI 0.35-0.82) and advanced disease stage (CDR ≥ 1 vs CDR 0: OR 11.11, 95% CI 2.0-50.0; vs CDR 0.5: OR 4.55, 95% CI 1.12-16.67) were independently associated with FP results.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.