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Tailoring thresholds for interpreting plasma p-tau217 levels

Ahn, Jehyun; Lee, Eun Hye; Yoo, Heejin; Shin, Daeun; Kang, Heekyoung; Yim, Sohyun; Kim, Seongmi; ... K-ROAD study group; + view all (2025) Tailoring thresholds for interpreting plasma p-tau217 levels. Journal of Neurology, Neurosurgery and Psychiatry 10.1136/jnnp-2025-335830. Green open access

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Abstract

BACKGROUND: 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. METHODS: 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. RESULTS: 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%. CONCLUSION: 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.

Type: Article
Title: Tailoring thresholds for interpreting plasma p-tau217 levels
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1136/jnnp-2025-335830
Publisher version: https://doi.org/10.1136/jnnp-2025-335830
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: ALZHEIMER'S DISEASE, AMYLOID, BIOCHEMISTRY, DEMENTIA, PET
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Neurodegenerative Diseases
URI: https://discovery.ucl.ac.uk/id/eprint/10209959
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