{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T03:49:53Z","timestamp":1777952993456,"version":"3.51.4"},"reference-count":50,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2025,2,6]],"date-time":"2025-02-06T00:00:00Z","timestamp":1738800000000},"content-version":"vor","delay-in-days":5,"URL":"http:\/\/creativecommons.org\/licenses\/by\/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"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["CNS Neurosci Ther"],"published-print":{"date-parts":[[2025,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Alzheimer's disease (AD) is a common neurodegenerative disorder with a substantial genetic component. Despite advances in elucidating the genetic underpinnings of AD, much of its heritability remains unexplained. Discovering novel genetic variants and understanding their pathogenic roles are crucial challenges in AD research.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>This study aimed to identify pathogenic genes and elucidate their role in familial early\u2010onset AD (EOAD).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Blood samples from an EOAD pedigree and Sorbin and SH3 Domain\u2010Containing Protein 2 (\n                      <jats:italic>SORBS2<\/jats:italic>\n                      ) T189M transgenic mice were analyzed. Cognitive function was assessed via the Morris water maze (MWM). Protein expression was evaluated by western blotting, while amyloid\u2010\u03b2 (A\u03b2) levels were quantified via immunohistochemistry and enzyme\u2010linked immunosorbent assay. Inflammatory markers were measured using immunofluorescence and quantitative reverse transcription polymerase chain reaction (PCR). Neuronal morphology, including dendritic and spine alterations, was examined using Golgi staining.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We identified a novel\n                      <jats:italic>SORBS2<\/jats:italic>\n                      variant (c. 566C&gt;T, p. T189M) in a Han Chinese family, segregating with AD in a Mendelian fashion.\n                      <jats:italic>SORBS2<\/jats:italic>\n                      T189M transgenic mice exhibited cognitive deficits, cortical A\u03b2 accumulation, and an increased A\u03b242\/A\u03b240 ratio. Additionally, elevated levels of interleukin (IL)\u20101\u03b2, IL\u20106, tumor necrosis factor \u03b1 (TNF\u2010\u03b1), and ionized calcium\u2010binding adaptor molecule 1 (Iba1)\u2010positive microglia, along with neuronal loss, were observed in the brains of T189M mice.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      Our study suggest that the\n                      <jats:italic>SORBS2<\/jats:italic>\n                      T189M variant is a novel candidate causal mutation associated with familial AD in a Chinese pedigree, contributing to AD pathogenesis by promoting neuroinflammation and neuronal injury. Notably, this study is the first to establish a link between\n                      <jats:italic>SORBS2<\/jats:italic>\n                      mutations and AD.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/cns.70256","type":"journal-article","created":{"date-parts":[[2025,2,6]],"date-time":"2025-02-06T07:28:31Z","timestamp":1738826911000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["A Novel Missense Variant in\n                    <scp>SORBS2<\/scp>\n                    Is Causative With Familial Alzheimer's Disease"],"prefix":"10.1111","volume":"31","author":[{"given":"Qi","family":"Wang","sequence":"first","affiliation":[{"name":"Innovation Center for Neurological Disorders and Department of Neurology, Xuanwu Hospital Capital Medical University, National Clinical Research Center for Geriatric Diseases  Beijing People's Republic of 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