{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T05:59:52Z","timestamp":1785477592878,"version":"3.56.0"},"reference-count":57,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T00:00:00Z","timestamp":1779321600000},"content-version":"vor","delay-in-days":20,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T00:00:00Z","timestamp":1777593600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["alz-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Alzheimer's &amp;amp; Dementia"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>INTRODUCTION<\/jats:title>\n                    <jats:p>\n                      In Alzheimer's disease (AD), tau\u2013neurodegeneration (T\u2013N) mismatch has been proposed to reflect non\u2010AD processes such as transactive response DNA binding protein 43\u00a0\n                      <jats:styled-content>kDa<\/jats:styled-content>\n                      and vascular disease. We aimed to characterize the spatiotemporal trajectories of T\u2013N mismatch that may reflect non\u2010AD progression.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>We performed T\u2013N regression on 710 Alzheimer's Disease Neuroimaging Initiative participants using cortical thickness and 18F\u2010flortaucipir uptake across 20 cortical regions. SuStaIn, a data\u2010driven phenotype discovery and staging algorithm, was applied to standardized T\u2013N residuals in canonical (N\u223cT) and vulnerable (N\u00a0&gt;\u00a0T) cases.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>SuStaIn identified three vulnerable subtypes with distinct N\u00a0&gt;\u00a0T progression patterns. The posterior and anterior subtypes displayed different, but progressively diffuse mismatch patterns, while the limbic subtype exhibited temporal\u2013limbic progression. Subtypes and SuStaIn stages were associated with distinct clinical features. Their longitudinal trajectories aligned with SuStaIn inferred progression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION<\/jats:title>\n                    <jats:p>Findings support that T\u2013N mismatch progression captures specific co\u2010pathological processes.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/alz.71474","type":"journal-article","created":{"date-parts":[[2026,5,22]],"date-time":"2026-05-22T03:32:05Z","timestamp":1779420725000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Uncovering distinct spatiotemporal trajectories of T\u2010N mismatch subtypes with likely co\u2010pathology in Alzheimer's disease using event\u2010based modeling"],"prefix":"10.1002","volume":"22","author":[{"given":"Xueying","family":"Lyu","sequence":"first","affiliation":[{"name":"Department of Bioengineering University of Pennsylvania  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher A.","family":"Brown","sequence":"additional","affiliation":[{"name":"Department of Neurology University of Pennsylvania  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael Tran","family":"Duong","sequence":"additional","affiliation":[{"name":"Department of Radiology University of Pennsylvania  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma P.","family":"Fischer","sequence":"additional","affiliation":[{"name":"Neuroscience Graduate Group Medicine University of Pennsylvania  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily","family":"McGrew","sequence":"additional","affiliation":[{"name":"Department of Radiology University of Pennsylvania  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David J.","family":"Irwin","sequence":"additional","affiliation":[{"name":"Department of Neurology University of Pennsylvania  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bradford C.","family":"Dickerson","sequence":"additional","affiliation":[{"name":"Massachusetts General Hospital  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilya M.","family":"Nasrallah","sequence":"additional","affiliation":[{"name":"Department of Radiology University of Pennsylvania  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Russell Takeshi","family":"Shinohara","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, Epidemiology and Informatics University of Pennsylvania  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra 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