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Among blood\u2010based biomarkers (BBMs), plasma phosphorylated tau217 (p\u2010tau217) has shown the highest accuracy, although intermediate (\u201cgray zone\u201d) values remain challenging to interpret.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>In this study, 401 individuals across the Alzheimer's Disease (AD) continuum (Subjective Cognitive Decline, Mild Cognitive Impairment, and AD dementia) underwent clinical and biomarker assessment. Plasma p\u2010tau217, p\u2010tau181, neurofilament light chain (NfL), and glial fibrillary acidic protein (GFAP) were measured. Core1 status was defined through CSF or amyloid\u2010PET.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>Plasma p\u2010tau217 demonstrated the strongest discrimination of Core1 positivity (area under the curve [AUC]\u00a0=\u00a00.95) and showed the steepest increase with disease progression. A two\u2010cutoff strategy improved diagnostic accuracy (94%), though 18% of patients fell into the gray zone. Within this subgroup, p\u2010tau181 was the only predictor of Core1 status and correctly reclassified 77.4% of indeterminate cases.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION<\/jats:title>\n                    <jats:p>These findings support a sequential plasma biomarkers approach for reliable AD detection.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/dad2.70285","type":"journal-article","created":{"date-parts":[[2026,2,15]],"date-time":"2026-02-15T09:05:38Z","timestamp":1771146338000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Refining Alzheimer's disease biological diagnosis with plasma biomarkers: Resolving p\u2010tau217 \u201cgray zone\u201d with p\u2010tau181 integration"],"prefix":"10.1002","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8711-331X","authenticated-orcid":false,"given":"Giulia","family":"Giacomucci","sequence":"first","affiliation":[{"name":"Department of Neuroscience, Psychology, Drug Research and Child Health University of Florence  Florence Italy"},{"name":"IRCCS Fondazione Don Carlo Gnocchi  Florence Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia Maria Rita","family":"Tabb\u00ec","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Psychology, Drug Research and Child Health University of Florence  Florence Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Assunta","family":"Ingannato","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Psychology, Drug Research and Child Health University of Florence  Florence Italy"},{"name":"IRCCS Fondazione Don Carlo Gnocchi  Florence 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Child Health University of Florence  Florence Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Serena","family":"Sanesi","sequence":"additional","affiliation":[{"name":"University of Florence  Florence Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentina","family":"Moschini","sequence":"additional","affiliation":[{"name":"Neurology Unit, Dipartimento Neuromuscoloscheletrico E Degli Organi Di Senso Careggi University Hospital  Florence Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmen","family":"Morinelli","sequence":"additional","affiliation":[{"name":"Neurology Unit, Dipartimento Neuromuscoloscheletrico E Degli Organi Di Senso Careggi University Hospital  Florence Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia","family":"Galdo","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Psychology, Drug Research and Child Health University of Florence  Florence 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