{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T14:22:58Z","timestamp":1786112578602,"version":"build-2736575974"},"reference-count":46,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T00:00:00Z","timestamp":1767830400000},"content-version":"vor","delay-in-days":7,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["JP23dk0207066"],"award-info":[{"award-number":["JP23dk0207066"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["JP22dk0207049"],"award-info":[{"award-number":["JP22dk0207049"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["R01AG071865"],"award-info":[{"award-number":["R01AG071865"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100020206","name":"Korea Dementia Research Center","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100020206","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003710","name":"Korea Health Industry Development Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003710","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000957","name":"Alzheimer's Association","doi-asserted-by":"publisher","award":["SG\u201020\u2010690363\u2010DIAN"],"award-info":[{"award-number":["SG\u201020\u2010690363\u2010DIAN"]}],"id":[{"id":"10.13039\/100000957","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":[[2026,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>INTRODUCTION<\/jats:title>\n                    <jats:p>Tau species lacking truncation of the N\u2010terminal region, including plasma N\u2010terminal tau fragment 1 (NT1), have been previously associated with cognitive decline, neurodegeneration, and tau pathology in late\u2010onset sporadic Alzheimer's disease (AD).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>Here, we examined cross\u2010sectional and longitudinal plasma NT1 as a possible predictor of cognitive, clinical, and core AD biomarker trajectories in autosomal dominant AD (ADAD).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      NT1 levels in ADAD mutation carriers (MC;\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a0132) increased across the disease continuum, compared to non\u2010carriers (NC;\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a075), becoming elevated about a decade prior to estimated symptom onset. Cross\u2010sectional and longitudinal NT1 levels in MC were associated with clinical, cognitive, and biomarker changes. NT1 increases continued in symptomatic phases of disease, a distinct trajectory from that seen with CSF p\u2010tau217 and other phospho\u2010tau species.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION<\/jats:title>\n                    <jats:p>Together, our results suggest that plasma NT1\u2014alone or combined with other tau measures\u2014may be useful in studying AD\u2010related clinical, cognitive, and biomarker outcomes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Highlights<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>Leveraging a deeply phenotyped cohort of individuals carrying a pathogenic variant for autosomal dominant Alzheimer's disease (ADAD) and their non\u2010carrier family members, our results suggest that plasma N\u2010terminal tau fragment 1 (NT1) levels mirrored changes in clinical, cognitive, and neurodegenerative measures in ADAD, particularly in late asymptomatic and early symptomatic phases of disease.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>NT1 levels correlated with cerebrospinal fluid (CSF) measures of tau pathology but less so with CSF or imaging measures of \u03b2\u2010amyloid pathology.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Together with previous supportive findings in preclinical and symptomatic sporadic AD, these results suggest that plasma NT1\u2014alone or combined with other tau measures\u2014may be useful in studying AD\u2010related tau pathology and neurodegeneration across a wide spectrum of disease.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/alz.71049","type":"journal-article","created":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T17:04:51Z","timestamp":1767891891000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Plasma levels of an N\u2010terminal tau fragment predict Alzheimer's and neurodegenerative disease biomarkers in autosomal dominant Alzheimer's disease"],"prefix":"10.1002","volume":"22","author":[{"given":"Stephanie A.","family":"Schultz","sequence":"first","affiliation":[{"name":"Department of Neurology Massachusetts General Hospital Boston Massachusetts USA"},{"name":"Department of Neurology Harvard Medical School Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiwen","family":"Rao","sequence":"additional","affiliation":[{"name":"Department of Neurology Brigham and Women's Hospital Boston 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Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wai\u2010Ying Wendy","family":"Yau","sequence":"additional","affiliation":[{"name":"Department of Neurology Massachusetts General Hospital Boston Massachusetts USA"},{"name":"Department of Neurology Harvard Medical School Boston Massachusetts USA"},{"name":"Department of Neurology Brigham and Women's Hospital Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zahra","family":"Shirzadi","sequence":"additional","affiliation":[{"name":"Department of Neurology Massachusetts General Hospital Boston Massachusetts USA"},{"name":"Department of Neurology Harvard Medical School Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian A.","family":"Gordon","sequence":"additional","affiliation":[{"name":"Washington University in St. Louis School of Medicine  St. Louis Missouri 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Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolas R.","family":"Barth\u00e9lemy","sequence":"additional","affiliation":[{"name":"Washington University in St. Louis School of Medicine  St. Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nick","family":"Fox","sequence":"additional","affiliation":[{"name":"Dementia Research Centre &amp; UK Dementia Research Institute UCL Institute of Neurology  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory S.","family":"Day","sequence":"additional","affiliation":[{"name":"Department of Neurology Mayo Clinic Jacksonville Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mathias","family":"Jucker","sequence":"additional","affiliation":[{"name":"Department of Cellular Neurology German Center for Neurodegenerative Diseases T\u00fcbingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allan 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