{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T20:21:00Z","timestamp":1793132460739,"version":"4.5.0"},"reference-count":27,"publisher":"Springer Science and Business Media LLC","issue":"6","license":[{"start":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T00:00:00Z","timestamp":1778198400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T00:00:00Z","timestamp":1778198400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100007642","name":"Universit\u00e0 degli Studi di Roma Tor Vergata","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100007642","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Neurol"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Anti-amyloid monoclonal antibodies have increased the need for scalable, minimally invasive biomarkers for Alzheimer\u2019s disease (AD). In this single-center cohort study, we evaluated plasma biomarkers performance in detecting biologically defined AD, assessing diagnostic accuracy and generalizability outside dedicated laboratory settings and exploring suitability for clinical implementation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We enrolled 204 outpatients referred to the memory clinic of Policlinico \u201cRome Tor Vergata\u201d who underwent standard work-up, lumbar puncture for cerebrospinal fluid (CSF) biomarkers and paired blood sampling. Among plasma biomarkers, phosphorylated tau (p-tau) 181, p-tau217, and their ratios adjusted for A\u03b242 were measured on the Lumipulse platform. AD pathology was defined by CSF p-tau181\/A\u03b242\u2009\u2265\u20090.069. ROC analyses estimated AUCs, and a two-cut-off approach targeting 90% sensitivity and specificity classified individuals as low, intermediate, or high AD risk. Subgroup analyses examined the impact of sex, age (&lt;\u200975,\u2009\u2265\u200975\u00a0years), chronic kidney disease, and cognitive impairment (MMSE\u2009\u2265\u200926\/30,\u2009&lt;\u200926\/30) on plasma biomarker levels.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Among single analytes, plasma p-tau217 showed the highest discriminative capacity (AUC 0.883). Combined ratios improved overall performance (p-tau181\/A\u03b242, AUC 0.928; p-tau217\/A\u03b242, AUC 0.894) and reduced intermediate-risk classifications to\u2009&lt;\u200915%, with slightly better performance in women, patients\u2009&lt;\u200975 and cognitively unimpaired. The two-cut-off model improved accuracy and rule-in ability.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>Plasma p-tau\/A\u03b242 ratios show high and robust accuracy for detecting CSF-defined AD pathology. A two-step approach based on p-tau181\/A\u03b242 or p-tau217\/A\u03b242 could streamline diagnostic workflows in memory clinics, reserving second-line assessments to indeterminate cases and supporting selection of candidates for disease-modifying anti-amyloid therapies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s00415-026-13833-x","type":"journal-article","created":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T04:12:52Z","timestamp":1778213572000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Streamlining Alzheimer\u2019s disease diagnosis: real-world validation of two-cut-off diagnostic models based on plasma p-tau\/A\u03b242 ratios"],"prefix":"10.1007","volume":"273","author":[{"given":"Martina","family":"Poli","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara Giuseppina","family":"Bonomi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martina Gaia","family":"Di Donna","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilaria","family":"Barberis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emanuele Luca","family":"Ginevra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marzia","family":"Nuccetelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergio","family":"Bernardini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diego","family":"Centonze","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"Martorana","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6734-6979","authenticated-orcid":false,"given":"Caterina","family":"Motta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,5,8]]},"reference":[{"key":"13833_CR1","doi-asserted-by":"publisher","first-page":"535","DOI":"10.1016\/j.jalz.2018.02.018","volume":"14","author":"CR Jack","year":"2018","unstructured":"Jack CR, Bennett DA, Blennow K et al (2018) NIA-AA research framework: toward a biological definition of Alzheimer\u2019s disease. 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Plasma AD biomarkers analysis was conducted with the approval of the local ethical committee (reference 134.24CET2ptv). All individuals involved in this study agreed to participate and to have results of the research about them published.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}}],"article-number":"306"}}