1. ⁸Department of Neurology, Soonchunhyang University Hospital Bucheon, Bucheon-si, Korea (the Republic of)
2. ⁹Neurology, Seoul National University Hospital, Jongno-gu, Korea (the Republic of)
3. ¹⁰Department of Digital Health, SAIHST, Sungkyunkwan University, Jongno-gu, Korea (the Republic of)
4. ¹¹Biomedical Statistics Center, Research Institute for Future Medicine, Samsung Medical Center, Gangnam-gu, Korea (the Republic of)

1. Correspondence to Professor Sang Won Seo; sw72.seo{at}samsung.com; Professor Kyunga Kim; kyunga.j.kim{at}samsung.com

Plasma phosphorylated tau (p-tau) 217 test has emerged as a minimally invasive and accessible alternative to positron emission tomography imaging and cerebrospinal fluid analysis for Alzheimer’s disease (AD) diagnostics. However, the diagnostic performance of p-tau217 across diverse cognitive and demographic subgroups remains underexplored. This multicentre cross-sectional study aimed to assess the diagnostic utility of plasma p-tau217 using a double cut-off approach in a large, diverse cohort, focusing on subgroup analyses based on cognitive status, age, sex, body mass index and APOE ε4 carrier status.

Plasma p-tau217 levels were analysed in cognitively unimpaired (CU) and cognitively impaired (CI) individuals. Double cut-offs for p-tau217 levels were selected to classify participants into amyloid-negative, intermediate and amyloid-positive groups. Diagnostic performance metrics including sensitivity, specificity, positive predictive value and negative predictive value were evaluated across subgroups, and tailored cut-off strategies were explored for specific populations.

The optimal cut-offs differed between CU and CI groups. In the CI group, diagnostic accuracy was consistently high across all subgroups, meeting confirmatory test standards with sensitivity and specificity ≥90%. In the CU group, the appropriate standards varied by subgroup. Participants aged <65 years required alternative cut-offs to improve sensitivity to 85.0% and maintain specificity at 95.7%.

Plasma p-tau217 demonstrated robust diagnostic accuracy across CI subgroups and highlighted the importance of tailored cut-off thresholds for CU populations. These findings support the integration of plasma p-tau217 into clinical workflows for AD diagnostics, emphasising its potential for early detection and risk stratification.

Data are available upon reasonable request. The anonymised data for the analyses presented in this report are available upon request from the corresponding authors.