Plasma p-tau217 in real-world clinical practice: distribution across clinical diagnostic categories, clinician confidence, and impact on care pathways

Plasma phosphorylated tau at threonine 217 (p-tau217) is a highly accurate blood-based biomarker for Alzheimer’s disease pathology, but evidence regarding its determinants and clinical impact in routine practice remains limited. We evaluated its distribution across real-world clinical phenotypes, biological determinants, and impact on diagnostic pathways. Between January and December 2025, we analyzed 1,368 consecutive patients undergoing plasma p-tau217 testing as part of routine evaluation for cognitive disorders across 24 participating centers in secondary and tertiary care settings. Diagnostic hypotheses were categorized as suspected Alzheimer’s disease, suspected non-Alzheimer cognitive disorders, or cognitive impairment without a specific etiological hypothesis. Plasma p-tau217 was categorized as negative, equivocal, or positive using predefined cut-offs. Associations with age, sex, cognitive status, renal function, and diagnostic group were assessed using descriptive statistics and multivariable models. Available paired CSF biomarker data were retrospectively analyzed. Clinical implementation was evaluated through a prescriber survey and objective activity data. Among 1,368 patients, 997 had suspected Alzheimer’s disease, 180 suspected non-Alzheimer cognitive disorders, and 191 no specific etiological hypothesis. Plasma p-tau217 positivity was higher in suspected Alzheimer’s disease than in suspected non-Alzheimer conditions (66.1% versus 17.8%), whereas patients without a specific hypothesis showed an intermediate distribution. Equivocal results occurred in 19.9% and were more frequent in older individuals. Plasma p-tau217 concentrations increased with age, were higher in women, were inversely correlated with MMSE and renal function, and differed across diagnostic groups. In 117 patients with paired plasma and CSF data, plasma p-tau217 correlated with the CSF p-tau181/Aβ42 ratio (Spearman ρ = 0.640) and showed good discrimination for a positive ratio (> 0.10; AUC = 0.870). Among 53 prescribers, 71% reported increased confidence in plasma p-tau217 since starting to use it, 80% shorter diagnostic delay, and 63% reduced use of brain fluorodeoxyglucose positron emission tomography. Cerebrospinal fluid biomarker requests decreased by approximately 46% between January–June 2024 and July–December 2025. In real-world clinical practice, plasma p-tau217 showed distinct distributions across clinical phenotypes and was associated with measurable changes in diagnostic pathways. Interpretation should integrate patient-specific factors, including age and renal function, together with the clinical context and pre-test probability.