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We investigated when it becomes detectable and whether it differs according to fluid amyloid and phosphorylated-tau (A\/T1) biomarker profiles.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We studied 292 individuals &lt;65\u00a0years who underwent 3T structural MRI and cerebrospinal fluid assessment of A\u03b242\/40 and\n                      <jats:italic>p<\/jats:italic>\n                      -tau181. Participants were classified as A\u2212T1\u2212 subjective cognitive decline (SCD; reference group), A+T1\u2212, or A+T1+. Cortical thickness and hippocampal volume were measured using FreeSurfer. EOAD signature regions were defined by comparing biomarker-confirmed AD dementia with the reference group and subsequently examined across A\/T1 profiles in SCD and mild cognitive impairment (MCI). Brain\u2013cognition associations were assessed.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The cohort comprised 107 reference and 185 amyloid-positive participants (76 A+T1\u2212 and 109 A+T1+). EOAD dementia was characterized by marked cortical thinning in posterior parietal and lateral temporal regions. In MCI, cortical thinning was focal in A+T1\u2212, but more extensive in A+T1+ who also showed hippocampal atrophy. At the SCD stage, focal thinning of the EOAD signature, precuneus, and banks of the superior temporal sulcus was observed in A+T1+, whereas no structural alterations were detected in A+T1\u2212. Cortical thinning was associated with episodic and visuospatial memory performance in MCI, while no brain\u2013cognition associations were observed in SCD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      EOAD-related cortical thinning is detectable before dementia and varies across A\/T1 profiles, with combined amyloid and\n                      <jats:italic>p<\/jats:italic>\n                      -tau181 positivity associated with earlier and more extensive structural involvement.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s00415-026-14187-0","type":"journal-article","created":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T01:49:41Z","timestamp":1791337781000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Cortical thickness signature of early-onset Alzheimer\u2019s disease across clinical stages and A\/T1 biomarker profiles"],"prefix":"10.1007","volume":"273","author":[{"given":"Alessandro","family":"Zilioli","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosaleena","family":"Mohanty","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Rosenberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Matton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tobias","family":"Granberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G\u00f6ran","family":"Hagman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Spallazzi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miia","family":"Kivipelto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3115-2977","authenticated-orcid":false,"given":"Eric","family":"Westman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,10,7]]},"reference":[{"key":"14187_CR1","doi-asserted-by":"publisher","first-page":"793","DOI":"10.1016\/S1474-4422(10)70159-9","volume":"9","author":"MN Rossor","year":"2010","unstructured":"Rossor MN, Fox NC, Mummery CJ et al (2010) The diagnosis of young-onset dementia. 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