{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T12:13:26Z","timestamp":1783944806876,"version":"3.55.0"},"reference-count":21,"publisher":"SAGE Publications","issue":"3","license":[{"start":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T00:00:00Z","timestamp":1772755200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"name":"the Guidance Project of the Scientific Research Program of Hubei Provincial Department of Education","award":["B2019233"],"award-info":[{"award-number":["B2019233"]}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Alzheimer\u2019s Disease"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Alzheimer's disease (AD) is a progressive neurodegenerative disorder with poorly understood molecular mechanisms and limited early detection biomarkers.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To identify genes causally associated with AD risk using reverse transcriptome-wide Mendelian randomization (revTWMR) and bulk RNA-sequencing (RNA-seq).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We analyzed publicly available RNA-seq data from peripheral blood samples of patients with clinically diagnosed AD and cognitively normal controls, obtained from the GEO database. Differential expression analysis was performed to identify differentially expressed genes (DEGs). We used revTWMR by integrating genome-wide association study (GWAS) summary statistics with expression quantitative trait loci (eQTL) data to infer causal relationships between gene expression and AD risk.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Using RNA-seq data from peripheral blood samples of AD patients and cognitively normal controls, we identified 126 DEGs. Through revTWMR analysis, we narrowed down to 91 genes with significant causal associations with AD, and further prioritized 5 genes with strong causal effects (|\u03b1|\u2009\u2265\u20090.8). Among these, PSMA6, CD19, and CMTM6 have potential roles in AD pathogenesis and may serve as promising blood-based biomarkers for early detection and therapeutic targeting.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our findings highlight the utility of revTWMR in identifying causally relevant genes in AD and suggest several blood-based candidate biomarkers for early detection and therapeutic development. This integrative approach provides novel insights into the molecular underpinnings of AD.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/13872877261422501","type":"journal-article","created":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T10:55:42Z","timestamp":1773226542000},"page":"1295-1303","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Identification of causally linked blood biomarkers for Alzheimer's disease via reverse transcriptome-wide Mendelian randomization"],"prefix":"10.1177","volume":"110","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-1292-5039","authenticated-orcid":false,"given":"Zimo","family":"Li","sequence":"first","affiliation":[{"name":"School of Medicine, Jianghan University, Wuhan, Hubei, \rChina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-9827-8839","authenticated-orcid":false,"given":"Dong","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Medicine, Jianghan University, Wuhan, Hubei, \rChina"},{"name":"School of Medicine, Jianghan University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5469-6785","authenticated-orcid":false,"given":"Fei","family":"Xia","sequence":"additional","affiliation":[{"name":"School of Medicine, Jianghan University, Wuhan, Hubei, \rChina"},{"name":"Hubei No. 3 People's Hospital of Jianghan University, Wuhan, Hubei, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7775-2671","authenticated-orcid":false,"given":"Yuchen","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Medicine, Jianghan University, Wuhan, Hubei, \rChina"},{"name":"Cancer Institute of Jianghan University, Wuhan, Hubei, China"},{"name":"Jianghan University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8002-383X","authenticated-orcid":false,"given":"Yunyi","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Medicine, Jianghan University, Wuhan, Hubei, \rChina"},{"name":"Cancer Institute of Jianghan University, Wuhan, Hubei, 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