{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T03:11:30Z","timestamp":1793416290244,"version":"4.5.0"},"reference-count":62,"publisher":"SAGE Publications","issue":"4","license":[{"start":{"date-parts":[[2025,3,17]],"date-time":"2025-03-17T00:00:00Z","timestamp":1742169600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"name":"the National Natural Science Foundation of China (NSFC)\/RGC Joint Research Scheme","award":["32061160472"],"award-info":[{"award-number":["32061160472"]}]},{"name":"the National Key R&D Program of China","award":["2021YFE0203000"],"award-info":[{"award-number":["2021YFE0203000"]}]},{"name":"the Guangdong Provincial Fund for Basic and Applied Basic Research","award":["2019B1515130004"],"award-info":[{"award-number":["2019B1515130004"]}]},{"name":"the Guangdong Provincial Key S&T Program","award":["2018B030336001"],"award-info":[{"award-number":["2018B030336001"]}]},{"name":"the Technology Innovation Commission of Shenzhen","award":["JCYJ20200109115631248, JCYJ20220818100800001, and ZDSYS20200828154800001"],"award-info":[{"award-number":["JCYJ20200109115631248, JCYJ20220818100800001, and ZDSYS20200828154800001"]}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Alzheimer\u2019s Disease"],"published-print":{"date-parts":[[2025,4]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Alzheimer's disease (AD) is a complex neurodegenerative disorder with intricate pathophysiological mechanisms. Transcriptome analysis has been used to investigate the pathogenesis of AD from the perspectives of mRNA expression, alternative splicing, and alternative polyadenylation. However, these 3 transcriptomic regulatory layers have not been comprehensively explored, limiting our understanding of the transcriptomic landscapes of AD pathogenesis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>We aimed to describe the transcriptomic landscapes of AD pathogenesis, detect the contributions of different regulatory layers to the total transcriptional variance, and identify diagnostic candidates for AD prediction.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We collected RNA sequencing data derived from the temporal lobes of 257 patients with AD and 97 controls, performed joint transcriptional analysis with multi-omics factor analysis (MOFA2) and weighted gene co-expression network analysis (WGCNA), and evaluated the signals with regression models.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We found that increasing Braak stage is associated with progressive downregulation of\n                      <jats:italic>SYT1, CHN1, SNAP25, VSNL1,<\/jats:italic>\n                      and\n                      <jats:italic>ENC1<\/jats:italic>\n                      as well as upregulation of\n                      <jats:italic>TNS1<\/jats:italic>\n                      ,\n                      <jats:italic>SGK1<\/jats:italic>\n                      ,\n                      <jats:italic>CPM<\/jats:italic>\n                      ,\n                      <jats:italic>PPFIBP<\/jats:italic>\n                      , and\n                      <jats:italic>CLMN<\/jats:italic>\n                      . Subsequent MOFA2 revealed that alternative splicing contributes most (\n                      <jats:italic>R<\/jats:italic>\n                      <jats:sup>2\u2009<\/jats:sup>\n                      =\u20090.558) to the transcriptional variance between patients with AD and controls followed by alternative polyadenylation (\n                      <jats:italic>R<\/jats:italic>\n                      <jats:sup>2\u2009<\/jats:sup>\n                      =\u20090.449) and mRNA expression (\n                      <jats:italic>R<\/jats:italic>\n                      <jats:sup>2\u2009<\/jats:sup>\n                      =\u20090.438). In addition, the regression model constructed with\n                      <jats:italic>SNAP25<\/jats:italic>\n                      ,\n                      <jats:italic>VSNL1<\/jats:italic>\n                      , and\n                      <jats:italic>ENC1<\/jats:italic>\n                      expression could distinguish between patients with AD and controls (AUC\u2009=\u20090.752).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>We systematically detailed the transcriptional landscapes in patients with AD and report mRNA signals associated with AD, offering novel insights into AD pathogenesis and therapeutic development.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/13872877251322536","type":"journal-article","created":{"date-parts":[[2025,3,17]],"date-time":"2025-03-17T12:21:46Z","timestamp":1742214106000},"page":"1075-1091","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":1,"title":["Changes in transcriptional regulation in the temporal lobe in patients with Alzheimer's disease"],"prefix":"10.1177","volume":"104","author":[{"given":"Yujie","family":"Yang","sequence":"first","affiliation":[{"name":"Chinese Academy of Sciences Key Laboratory of Brain Connectome and Manipulation, Shenzhen Key Laboratory of Translational Research for Brain Diseases, The Brain Cognition and Brain Disease Institute, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research Institutions, Shenzhen, China"},{"name":"University of Chinese Academy of Sciences, Beijing, China"},{"name":"SIAT-HKUST Joint Laboratory for Brain Science, Chinese Academy of Sciences, Shenzhen, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yinhu","family":"Li","sequence":"additional","affiliation":[{"name":"Chinese Academy of Sciences Key Laboratory of Brain Connectome and Manipulation, Shenzhen Key Laboratory of Translational Research for Brain Diseases, The Brain Cognition and Brain Disease Institute, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research Institutions, Shenzhen, China"},{"name":"SIAT-HKUST Joint Laboratory for Brain Science, Chinese Academy of Sciences, Shenzhen, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7569-9472","authenticated-orcid":false,"given":"Yu","family":"Chen","sequence":"additional","affiliation":[{"name":"Chinese Academy of Sciences Key Laboratory of Brain Connectome and Manipulation, Shenzhen Key Laboratory of Translational Research for Brain Diseases, The Brain Cognition and Brain Disease Institute, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research Institutions, Shenzhen, China"},{"name":"University of Chinese Academy of Sciences, Beijing, China"},{"name":"SIAT-HKUST Joint Laboratory for Brain Science, Chinese Academy of Sciences, Shenzhen, China"},{"name":"Guangdong Provincial Key Laboratory of Brain Science, Disease and Drug Development, HKUST Shenzhen Research Institute, Shenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research Institutions, Shenzhen, Guangdong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2025,3,17]]},"reference":[{"key":"e_1_3_5_2_2","doi-asserted-by":"publisher","DOI":"10.1186\/alzrt59"},{"key":"e_1_3_5_3_2","doi-asserted-by":"publisher","DOI":"10.1002\/med.21719"},{"key":"e_1_3_5_4_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13195-020-00755-7"},{"key":"e_1_3_5_5_2","first-page":"6","article-title":"Alternative splicing in Alzheimer's disease","volume":"2","author":"Love JE","year":"2015","unstructured":"Love JE, Hayden EJ, Rohn TT. 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