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

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.

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.

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).

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