{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T12:08:36Z","timestamp":1789560516176,"version":"build-2803163510"},"reference-count":64,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2025,2,5]],"date-time":"2025-02-05T00:00:00Z","timestamp":1738713600000},"content-version":"vor","delay-in-days":4,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2025,2,1]],"date-time":"2025-02-01T00:00:00Z","timestamp":1738368000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100012149","name":"National Key Scientific Instrument and Equipment Development Projects of China","doi-asserted-by":"publisher","award":["31627803"],"award-info":[{"award-number":["31627803"]}],"id":[{"id":"10.13039\/501100012149","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":[[2025,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>INTRODUCTION<\/jats:title>\n                    <jats:p>Research on somatic and germline mutations in Chinese individuals with early\u2010onset Alzheimer's disease (EOAD) has been limited.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>We conducted whole\u2010genome sequencing of blood DNA from 108 patients with EOAD and 116 controls. The analysis included somatic and germline mutations across coding and non\u2010coding regions, mutational signature determination, pathway enrichment identification, and predictive model.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      The mutational burden was significantly higher in the EOAD group compared to the control group. The prevalence of single\u2010base substitution signature 5, which is strongly associated with aging, was much higher in patients with EOAD than in controls. EOAD\u2010specific somatic mutations were identified in genes such as\n                      <jats:italic>MIR31HG<\/jats:italic>\n                      ,\n                      <jats:italic>TUBB4B<\/jats:italic>\n                      , and\n                      <jats:italic>APP<\/jats:italic>\n                      . Germline mutations in\n                      <jats:italic>DOCK3<\/jats:italic>\n                      ,\n                      <jats:italic>PCSK5<\/jats:italic>\n                      , and\n                      <jats:italic>PDE4D<\/jats:italic>\n                      were significantly associated with age of dementia onset. Furthermore, a predictive model comprising 15 mutations demonstrated an area under the curve of 0.78.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION<\/jats:title>\n                    <jats:p>The accumulation of senescence\u2010related somatic mutations may increase the risk of developing EOAD.<\/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>Whole genome sequencing was used to find somatic and germline mutations in Chinese individuals with early\u2010onset Alzheimer's disease (EOAD).<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Total number and burden of blood somatic mutations were significantly higher.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>The prevalence of single\u2010base substitution signature 5 was notably elevated in EOAD.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>\n                            EOAD\u2010specific somatic mutations were identified in\n                            <jats:italic>MIR31HG<\/jats:italic>\n                            ,\n                            <jats:italic>TUBB4B<\/jats:italic>\n                            , and\n                            <jats:italic>APP<\/jats:italic>\n                            .\n                          <\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>\n                            <jats:italic>DOCK3<\/jats:italic>\n                            ,\n                            <jats:italic>PCSK5<\/jats:italic>\n                            , and\n                            <jats:italic>PDE4D<\/jats:italic>\n                            germline mutations were associated with the age of EOAD onset.\n                          <\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/alz.14486","type":"journal-article","created":{"date-parts":[[2025,2,5]],"date-time":"2025-02-05T07:07:41Z","timestamp":1738739261000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["The genetic landscape of early\u2010onset Alzheimer's disease in China"],"prefix":"10.1002","volume":"21","author":[{"given":"Wei","family":"Qin","sequence":"first","affiliation":[{"name":"Innovation Center for Neurological Disorders and Department of Neurology, Xuanwu 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