{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,26]],"date-time":"2025-09-26T08:07:15Z","timestamp":1758874035857,"version":"3.41.2"},"reference-count":41,"publisher":"Wiley","issue":"20","license":[{"start":{"date-parts":[[2024,10,29]],"date-time":"2024-10-29T00:00:00Z","timestamp":1730160000000},"content-version":"vor","delay-in-days":28,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Cellular Molecular Medi"],"published-print":{"date-parts":[[2024,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Neuroinflammation is increasingly recognized as a pivotal factor in the development and progression of neurodegenerative disorders. While correlations between inflammatory cytokines and these diseases are documented, the definitive causal dynamics remain to be elucidated. We explored the causal association between 91 circulating inflammatory cytokines and Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS) and Parkinson's disease (PD) through Mendelian randomization analysis. Leveraging genetic variants from the most comprehensive genome\u2010wide association studies (GWAS) available for these cytokines, AD, ALS, MS and PD, we sought to uncover the causality. Our study validated a causal influence of genetically determined cytokine levels on the susceptibility to AD, with notable cytokines including C\u2010X\u2010C motif chemokine 1 (OR\u2009=\u20090.9993, <jats:italic>p<\/jats:italic>\u2009=\u20090.0424), Interleukin\u201018 (OR\u2009=\u20090.9994, <jats:italic>p<\/jats:italic>\u2009=\u20090.0186), Leukaemia inhibitory factor receptor (OR\u2009=\u20090.9993, <jats:italic>p<\/jats:italic>\u2009=\u20090.0122) and Monocyte chemoattractant protein\u20101 (OR\u2009=\u20090.9992, <jats:italic>p<\/jats:italic>\u2009=\u20090.0026) in risk attenuation. Additionally, a positive causal relationship was identified between two cytokines\u2014C\u2010C motif chemokine 19 (OR\u2009=\u20091.0005, <jats:italic>p<\/jats:italic>\u2009=\u20090.0478) and Fms\u2010related tyrosine kinase 3 ligand (OR\u2009=\u20091.0005, <jats:italic>p<\/jats:italic>\u2009=\u20090.0210)\u2014and AD incidence. Conversely, transforming growth factor\u2010alpha (OR\u2009=\u20090.8630, <jats:italic>p<\/jats:italic>\u2009=\u20090.0298), CD40L receptor (OR\u2009=\u20090.7737, <jats:italic>p<\/jats:italic>\u2009=\u20091.1265E\u201009) and Interleukin\u201012 subunit beta (OR\u2009=\u20090.8987, <jats:italic>p<\/jats:italic>\u2009=\u20090.0333) showed inverse associations with ALS, MS and PD, respectively. The consistency observed in various MR analyses, alongside sensitivity analysis, underscored the absence of horizontal pleiotropy, thus supporting our causal findings. This study reveals, for the first time, a genetically anchored causal nexus between levels of circulating inflammatory cytokines and the risk of neurodegenerative diseases.<\/jats:p>","DOI":"10.1111\/jcmm.70176","type":"journal-article","created":{"date-parts":[[2024,10,29]],"date-time":"2024-10-29T14:42:36Z","timestamp":1730212956000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Causal association of circulating inflammatory proteins on neurodegenerative diseases: Insights from a mendelian randomization study"],"prefix":"10.1111","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4080-2078","authenticated-orcid":false,"given":"Wenwen","family":"Lin","sequence":"first","affiliation":[{"name":"Department of Pathology, Shenzhen Hospital Southern Medical University  Shenzhen Guangdong P. R. China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xuewei","family":"Wu","sequence":"additional","affiliation":[{"name":"National Clinical Research Center for Infectious Disease, The Third People's Hospital of Shenzhen Second Hospital Affiliated to Southern University of Science and Technology  Shenzhen Guangdong P. R. China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2761-522X","authenticated-orcid":false,"given":"Guanyong","family":"Ou","sequence":"additional","affiliation":[{"name":"National Clinical Research Center for Infectious Disease, The Third People's Hospital of Shenzhen Second Hospital Affiliated to Southern University of Science and Technology  Shenzhen Guangdong P. R. China"},{"name":"School of Medicine Southern University of Science and Technology  Shenzhen Guangdong P. R. 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