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However, their roles in neurodegenerative diseases, particularly Alzheimer\u2019s disease (AD), remain poorly understood. Recent evidence of an inverse association between cancer and AD suggests the existence of shared molecular mechanisms. We conducted an integrative analysis to identify TSGs with potential involvement in both AD and glioblastoma (GBM), using Mendelian randomization, transcriptomic profiling (bulk and single-cell RNA-seq), cell\u2013cell communication inference, and in vitro validation. Among 1,217 TSGs screened, <jats:italic>TNFRSF12A<\/jats:italic> was consistently dysregulated in both GBM and AD datasets. Further analysis revealed its association with immune-related pathways and transcriptional programs relevant to both diseases. Knockdown of <jats:italic>TNFRSF12A<\/jats:italic> in glioma cells altered the expression of genes associated with amyloid precursor protein (APP) processing and Wnt signaling pathways. This study identifies <jats:italic>TNFRSF12A<\/jats:italic> as a cross-disease candidate gene in GBM and AD, based on transcriptomic convergence and partial functional validation. Our findings suggest that TSGs may contribute to shared molecular programs in neurodegeneration and cancer, and warrant further mechanistic investigation.<\/jats:p>","DOI":"10.1038\/s41598-025-08000-7","type":"journal-article","created":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T17:58:20Z","timestamp":1751392700000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Potential role of TNFRSF12A in linking glioblastoma and alzheimer\u2019s disease via shared tumour suppressor pathways"],"prefix":"10.1038","volume":"15","author":[{"given":"Ting","family":"Liu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingjing","family":"Pu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"Theil","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanxia","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liping","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongde","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jarek","family":"Maciaczyk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ingo G. 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