Plasma Phosphorylated Tau 217 Reshapes Diagnostic Classification in a Real-World Memory Clinic Cohort.

Abstract

Background: Plasma phosphorylated tau-217 (ptau217) accurately identifies Alzheimer disease (AD), but its impact on real-world clinical diagnosis remains unclear. We evaluated the effect of plasma ptau217 on diagnostic reclassification in a memory disorders clinic.

Methods: We retrospectively reviewed 100 patients evaluated for memory impairment. Initial clinical diagnoses were established based on clinical evaluation, neuropsychological testing, and brain MRI without plasma biomarker results. Follow-up diagnoses were assigned after the availability of plasma ptau217 results. Diagnostic reclassification was assessed using binary (ptau217 > 0.18) and higher threshold (ptau217 > 0.325) classification schemes. McNemar tests evaluated reclassification patterns, with subgroup analyses by apolipoprotein E (APOE) ε4 carrier status.

Results: Diagnosis reclassification occurred in 37.8% and 46.9% of patients using the lower and higher threshold, respectively (both P<0.001). With the higher threshold (ptau217 > 0.325), reclassification among APOE ε4 carriers was balanced (42% from AD to non-AD vs. 43% from non-AD to AD, P=0.096). In contrast, APOE ε4 noncarriers showed significantly greater reclassification from AD to non-AD than from non-AD to AD (66% vs.14%, P<0.001).

Conclusions: Plasma ptau217 meaningfully influences diagnostic decisions in memory clinic practice and may be particularly valuable for refining diagnoses among APOE ε4 noncarriers.