{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T11:35:25Z","timestamp":1786707325982,"version":"build-2736575974"},"reference-count":50,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T00:00:00Z","timestamp":1786665600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Major and Special Projects of Fujian Province","award":["2020NZ010008"],"award-info":[{"award-number":["2020NZ010008"]}]},{"name":"High level Talent Innovation and Entrepreneurship Project of Quanzhou","award":["2022C006R"],"award-info":[{"award-number":["2022C006R"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Curr. Issues Mol. Biol.","CIMB"],"abstract":"<jats:p>Alzheimer\u2019s disease (AD) has a complex pathogenesis, involving molecular and neuroimmune dysregulation, but the causal drivers linking transcriptomic changes to immune remodeling are not yet clear. In a discovery cohort, differential expression analysis was performed, and it was independently validated in two external cohorts. Key genes were prioritized via LASSO\/logistic regression, functionally annotated, and causally linked to AD using two-sample MR. The neuroimmune landscape was mapped by ssGSEA, and top candidates were validated in vitro. RGS1 is a key node in neuroinflammation and cytoskeletal dynamics, which is prioritized by the algorithmic intersection. MR analysis suggested a potential causal association between genetically predicted RGS1 expression and AD risk. RGS1 was consistently upregulated in both discovery and validation cohorts (AUC: 0.61\u20130.67) and was confirmed in vitro. Immune deconvolution showed that AD-specific enrichment profiles occur, and RGS1 is strongly correlated with activated CD4+ T cells and pro-inflammatory chemokines. RGS1 is identified as a robust key gene that may contribute to immune microenvironment dysregulation in AD, and combining discovery-validation transcriptomics, causal inference, and experimental validation, we find that RGS1 is a potential immunomodulatory target.<\/jats:p>","DOI":"10.3390\/cimb48080828","type":"journal-article","created":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T10:39:01Z","timestamp":1786703941000},"page":"828","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Integrative Transcriptomics and Mendelian Randomization Identify RGS1 as a Causal Immune Regulator in Alzheimer\u2019s Disease"],"prefix":"10.3390","volume":"48","author":[{"given":"Zhiyun","family":"Cheng","sequence":"first","affiliation":[{"name":"School of Medicine, Huaqiao University, Quanzhou 362021, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruyu","family":"Bai","sequence":"additional","affiliation":[{"name":"School of Medicine, Huaqiao University, Quanzhou 362021, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0633-1906","authenticated-orcid":false,"given":"Yong","family":"Diao","sequence":"additional","affiliation":[{"name":"School of Medicine, Huaqiao University, Quanzhou 362021, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1374","DOI":"10.1177\/13872877251374149","article-title":"Harnessing nanoparticles for Alzheimer\u2019s disease: Innovations in drug delivery and pathology-specific treatments","volume":"107","author":"Liu","year":"2025","journal-title":"J. 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