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

Background: Plasma phosphorylated tau-217 (ptau217) has demonstrated accuracy exceeding 90% for Alzheimers disease (AD) diagnosis. While its diagnostic validity has been established, its real-world clinical utility in altering or corroborating clinician diagnoses remains less understood. This study evaluates the impact of plasma ptau217 on diagnostic reclassification in a memory disorders clinic. Methods: We conducted a retrospective chart review of 100 patients evaluated for memory impairment who subsequently underwent plasma biomarker testing. Initial clinical diagnoses were established using the National Institute of Neurological and Communicative Disorders and Stroke/Alzheimer Disease and Related Disorders Association criteria, neuropsychological testing, and brain magnetic resonance imaging without knowledge of plasma biomarker results. Follow-up diagnoses were assigned after the availability of plasma ptau217 or Precivity AD2 results. Diagnostic reclassification was evaluated under two p-tau217 classification schemes to determine the AD etiology: a binary cutoff with lower threshold (AD = ptau217 > 0.18) and a three-level cutoff incorporating a higher threshold (AD = ptau217 > 0.325). Reclassification matrices and McNemar's tests were used to assess changes in diagnosis. Subgroup analyses were conducted according to apolipoprotein E (APOE) {epsilon}4 carrier status. Results: The overall diagnosis reclassification rates were 37.8% (chi-square (1) = 10.81, p = 0.001) and 46.9% (chi-square (1) = 29.76; p < 0.001) using lower and higher threshold analyses, respectively. With the higher threshold (ptau217 > 0.325), reclassification among APOE {epsilon}4 carriers occurred in both directions at similar frequencies, without evidence of a net shift toward AD or non-AD (42% from AD to non-AD, 43% from non-AD to AD, chi-square (1) = 2.77 p = 0.096). Among {epsilon}4 non-carriers, reclassification was significantly asymmetric toward non-AD (66% from AD to non-AD, 14% from non-AD to AD, chi-square (1) = 16.41, p < 0.001), suggesting ptau217 may be identifying diagnostically heterogeneous cases in which the clinical presentation resembles AD but instead reflects an alternative or co-morbid etiologies. Conclusion: Plasma ptau217 meaningfully influences diagnostic decisions in a memory clinic setting and may be particularly valuable among APOE {epsilon}4 non-carriers, where biomarker-informed evaluation frequently shifted diagnoses away from AD.