{"corpus_id":218583348,"paper_sha":"244999c68e6f357ad88551ce4c8f0b3190742420","doi":"10.3233/JAD-200056","arxiv_id":null,"pmid":32390629,"pmcid":null,"mag_id":3023036454,"dblp_id":null,"acl_id":null,"title":"IL-1β, IL-6, IL-10, and TNFα Single Nucleotide Polymorphisms in Human Influence the Susceptibility to Alzheimer’s Disease Pathology","year":2020,"publication_date":"2020-05-04","venue":"Journal of Alzheimer's Disease","journal":{"name":"Journal of Alzheimer's Disease","pages":"1029 - 1047","volume":"75"},"journal_issn":null,"journal_title":null,"publication_types":["JournalArticle"],"pubmed_pub_types":["Journal Article","Research Support, N.I.H., Extramural","Research Support, Non-U.S. Gov't"],"s2_fields_of_study":["Biology","Medicine"],"reference_count":143,"citation_count":56,"influential_citation_count":1,"is_open_access":false,"arxiv_categories":null,"arxiv_license":null,"arxiv_journal_ref":null,"mesh_headings":[{"d":"Aged","mj":false,"ui":"D000368"},{"d":"Alzheimer Disease","mj":false,"qs":[{"q":"complications","mj":false,"ui":"Q000150"},{"q":"genetics","mj":true,"ui":"Q000235"},{"q":"pathology","mj":true,"ui":"Q000473"}],"ui":"D000544"},{"d":"Amyloid beta-Peptides","mj":false,"qs":[{"q":"cerebrospinal fluid","mj":false,"ui":"Q000134"}],"ui":"D016229"},{"d":"Biomarkers","mj":false,"qs":[{"q":"cerebrospinal fluid","mj":false,"ui":"Q000134"}],"ui":"D015415"},{"d":"Encephalitis","mj":false,"qs":[{"q":"complications","mj":false,"ui":"Q000150"},{"q":"genetics","mj":false,"ui":"Q000235"}],"ui":"D004660"},{"d":"Female","mj":false,"ui":"D005260"},{"d":"Genetic Predisposition to Disease","mj":false,"ui":"D020022"},{"d":"Genotype","mj":false,"ui":"D005838"},{"d":"Humans","mj":false,"ui":"D006801"},{"d":"Interleukin-10","mj":false,"qs":[{"q":"cerebrospinal fluid","mj":false,"ui":"Q000134"},{"q":"genetics","mj":true,"ui":"Q000235"}],"ui":"D016753"},{"d":"Interleukin-1beta","mj":false,"qs":[{"q":"cerebrospinal fluid","mj":false,"ui":"Q000134"},{"q":"genetics","mj":true,"ui":"Q000235"}],"ui":"D053583"},{"d":"Interleukin-6","mj":false,"qs":[{"q":"cerebrospinal fluid","mj":false,"ui":"Q000134"},{"q":"genetics","mj":true,"ui":"Q000235"}],"ui":"D015850"},{"d":"Male","mj":false,"ui":"D008297"},{"d":"Middle Aged","mj":false,"ui":"D008875"},{"d":"Polymorphism, Single Nucleotide","mj":false,"ui":"D020641"},{"d":"Tumor Necrosis Factor-alpha","mj":false,"qs":[{"q":"cerebrospinal fluid","mj":false,"ui":"Q000134"},{"q":"genetics","mj":true,"ui":"Q000235"}],"ui":"D014409"},{"d":"tau Proteins","mj":false,"qs":[{"q":"cerebrospinal fluid","mj":false,"ui":"Q000134"}],"ui":"D016875"}],"chemicals":[{"n":"Amyloid beta-Peptides","ui":"D016229","reg":"0"},{"n":"Biomarkers","ui":"D015415","reg":"0"},{"n":"IL10 protein, human","ui":"C508609","reg":"0"},{"n":"IL1B protein, human","ui":"C508585","reg":"0"},{"n":"Interleukin-1beta","ui":"D053583","reg":"0"},{"n":"Interleukin-6","ui":"D015850","reg":"0"},{"n":"MAPT protein, human","ui":"C054369","reg":"0"},{"n":"TNF protein, human","ui":"C439524","reg":"0"},{"n":"Tumor Necrosis Factor-alpha","ui":"D014409","reg":"0"},{"n":"tau Proteins","ui":"D016875","reg":"0"},{"n":"Interleukin-10","ui":"D016753","reg":"130068-27-8"}],"comments_corrections":null,"source_flags":5,"s2_open_access_pdf_url":null,"s2_open_access_landing_url":null,"s2_open_access_license":null,"s2_open_access_status":null,"pmc_open_access_pdf_url":null,"pmc_open_access_landing_url":null,"pmc_open_access_license":null,"pmc_open_access_status":null,"unpaywall_open_access_pdf_url":null,"unpaywall_open_access_landing_url":null,"unpaywall_open_access_license":null,"unpaywall_open_access_status":null,"abstract":"Background: Neuroinflammation plays an important role in Alzheimer’s disease (AD). During this process, activated microglia release pro-inflammatory cytokines such as interleukin (IL)-1α, IL-1β, IL-6, and tumor necrosis factor α (TNFα) that participate in neuron damage, but also anti-inflammatory cytokines (such as IL-10), which maintain homeostasis of immune response. Previous studies showed the association of IL-1α –889C/T (rs1800587), IL-1β–1473G/C (rs1143623), IL-6 –174C/G (rs1800795), IL-10 –1082G/A (rs1800896), and TNFα –308A/G (rs1800629) polymorphisms with AD. Objective: We aimed to investigate whether people with certain IL-1α, IL-1β, IL-6, IL-10, and TNFα genotypes in these polymorphisms are more prone to develop AD-related pathology, reflected by pathological levels of cerebrospinal fluid (CSF) AD biomarkers including amyloid-β1-42, total tau (t-tau), tau phosphorylated at Thr 181 (p-tau181), Ser 199 (p-tau199), and Thr 231 (p-tau231), and visinin-like protein 1 (VILIP-1). Methods: The study included 115 AD patients, 53 patients with mild cognitive impairment, and 11 healthy controls. The polymorphisms were determined using real-time polymerase chain reaction. Levels of CSF biomarkers were determined by enzyme-linked immunosorbent assay. Results: A significant increase in p-tau CSF levels was found in patients with the AA IL-10 –1082G/A and GG TNFα –308A/G genotypes, and in carriers of a G allele in IL-1β –1473C/G and IL-6 –174C/G polymorphisms. t-tau levels were increased in carriers of a G allele in IL-1β –1473C/G polymorphism. An increase in VILIP-1 levels was observed in patients with CG and GG IL-1β –1473C/G, GC IL-6 –174C/G, and GG TNFα –308A/G genotype. Conclusion: These results suggest that persons carrying certain genotypes in IL10 (–1082G/A), IL1β (1473C/G), IL6 (–174C/G), and TNFIα (–308A/G) could be more vulnerable to development of neuroinflammation, and consequently of AD.","claims":[{"public_id":"cl_300a91430012e610d9e9e4b255c86428","status":"active","text":"AA IL-10 –1082G/A and GG TNFα –308A/G genotypes are associated with increased p-tau cerebrospinal fluid levels.","confidence":0.94,"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/claims/cl_300a91430012e610d9e9e4b255c86428"},{"public_id":"cl_2749b7384998de114ce3181e719444bc","status":"active","text":"Carriers of the G allele in IL-1β –1473C/G and IL-6 –174C/G show increased p-tau cerebrospinal fluid levels.","confidence":0.94,"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous 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