{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,7]],"date-time":"2026-06-07T17:17:53Z","timestamp":1780852673790,"version":"3.54.1"},"reference-count":33,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2025,10,23]],"date-time":"2025-10-23T00:00:00Z","timestamp":1761177600000},"content-version":"vor","delay-in-days":22,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01AG061151"],"award-info":[{"award-number":["R01AG061151"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01AG055523"],"award-info":[{"award-number":["R01AG055523"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01AG070154"],"award-info":[{"award-number":["R01AG070154"]}],"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":[[2025,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>INTRODUCTION<\/jats:title>\n                    <jats:p>Alzheimer's disease (AD), the leading cause of dementia, is more common in females. Although sex differences in tau pathology have been reported in AD, findings remain inconsistent. Down syndrome (DS), caused by trisomy 21, is the most common genetic cause of AD (DS\u2010AD) and features tau pathology, but sex effects in DS\u2010AD remain unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>\n                      We examined\n                      <jats:italic>post mortem<\/jats:italic>\n                      brain samples from individuals with DS\u2010AD, DS without AD, and a rare partial trisomy 21 (PT) case with only two amyloid precursor protein (\n                      <jats:italic>APP<\/jats:italic>\n                      ) gene\ncopies. PHF1 tau, total tau, and sarkosyl\u2010soluble and insoluble fractions were quantified by group and sex.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>PHF1 tau was significantly elevated in DS\u2010AD, especially in females. Lower total tau in DS\u2010AD males explained the absence of sex differences after normalization. Sarkosyl\u2010insoluble tau was also higher in DS\u2010AD females. DS without AD, and the PT case showed minimal pathology.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION<\/jats:title>\n                    <jats:p>\n                      These findings suggest sex\u2010specific tau dynamics in DS\u2010AD and support a role for\n                      <jats:italic>APP<\/jats:italic>\n                      dosage.\n                    <\/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>Tau pathology is significantly elevated in individuals with DS\u2010AD, especially in females.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Female DS\u2010AD brains show markedly higher PHF1 (S396\/404) and sarkosyl\u2010insoluble tau levels compared to males.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>The observed sex difference in phosphorylated tau is driven by lower total tau in DS\u2010AD males.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Minimal tau pathology is present in DS without AD and in a rare partial trisomy 21 case.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>\n                            These findings implicate\n                            <jats:italic>APP<\/jats:italic>\n                            gene dosage in tau pathology in DS\u2010AD.\n                          <\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/alz.70838","type":"journal-article","created":{"date-parts":[[2025,10,23]],"date-time":"2025-10-23T10:49:15Z","timestamp":1761216555000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Tau pathology differs by sex in Alzheimer's disease in Down syndrome"],"prefix":"10.1002","volume":"21","author":[{"given":"Xu\u2010Qiao","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Neurosciences School of Medicine University of California San Diego  La Jolla California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinxin","family":"Zuo","sequence":"additional","affiliation":[{"name":"Department of Neurosciences School of Medicine University of California San Diego  La Jolla California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William 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