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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\n                      <jats:italic>APOE<\/jats:italic>\n                      \u03b54 carrier status.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>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 \u226590%. In the CU group, the appropriate standards varied by subgroup. Participants aged &lt;65 years required alternative cut-offs to improve sensitivity to 85.0% and maintain specificity at 95.7%.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/jnnp-2025-335830","type":"journal-article","created":{"date-parts":[[2025,5,24]],"date-time":"2025-05-24T21:30:18Z","timestamp":1748122218000},"page":"722-727","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":17,"title":["Tailoring thresholds for interpreting plasma p-tau217 levels"],"prefix":"10.1136","volume":"96","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-0927-6069","authenticated-orcid":false,"given":"Jehyun","family":"Ahn","sequence":"first","affiliation":[{"name":"Alzheimer\u2019s Disease Convergence Research Center, Samsung Medical Center, Gangnam-gu, Korea (the Republic 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