{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T20:30:07Z","timestamp":1786739407907,"version":"build-2736575974"},"reference-count":13,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"7","license":[{"start":{"date-parts":[[2019,7,1]],"date-time":"2019-07-01T00:00:00Z","timestamp":1561939200000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2019,7]]},"abstract":"<jats:p>\n                    Due to the aging of the population and despite the enormous scientific effort, Alzheimer\u2019s disease remains one of the biggest medical and pharmaceutical challenges in current medicine. Novel insights highlight the importance of neuroinflammation as an undeniable player in the onset and progression of Alzheimer\u2019s disease. Tumor necrosis factor is a master inflammatory cytokine that signals\n                    <jats:italic toggle=\"yes\">via<\/jats:italic>\n                    tumor necrosis factor receptor 1 and tumor necrosis factor receptor 2, but that also regulates several brain functions in health and disease. However, clinical trials investigating drugs that interfere with the tumor necrosis factor pathway in Alzheimer\u2019s disease led to inconclusive results, partially because not only the pro-inflammatory tumor necrosis factor\/tumor necrosis factor receptor 1, but also the beneficial tumor necrosis factor\/tumor necrosis factor receptor 2 signaling was antagonized in these trials. We recently found that tumor necrosis factor is the main upregulated cytokine in the choroid plexus of Alzheimer\u2019s disease patients, signaling\n                    <jats:italic toggle=\"yes\">via<\/jats:italic>\n                    tumor necrosis factor receptor 1. In agreement with this, choroidal tumor necrosis factor\/tumor necrosis factor receptor 1 signaling was also upregulated in different Alzheimer\u2019s disease mouse models. Interestingly, both genetic and nanobody-based pharmacological blockage of tumor necrosis factor receptor 1 signaling was accompanied by favorable effects on Alzheimer\u2019s disease-associated inflammation, choroidal morphology and cognitive functioning. Here, we briefly summarize the detrimental effects that can be mediated by tumor necrosis factor\/tumor necrosis factor receptor 1 signaling in (early) Alzheimer\u2019s disease, and the consequences this might have on the disease progression. As the main hypothesis in Alzheimer\u2019s disease clinical trials is still based on the amyloid beta-cascade, the importance of Alzheimer\u2019s disease-associated neuroinflammation urge the development of novel therapeutic strategies that might be effective in the early stages of Alzheimer\u2019s disease and prevent the irreversible neurodegeneration and resulting memory decline.\n                  <\/jats:p>","DOI":"10.4103\/1673-5374.247443","type":"journal-article","created":{"date-parts":[[2019,2,26]],"date-time":"2019-02-26T02:41:03Z","timestamp":1551148863000},"page":"1144-1147","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":12,"title":["Choroid plexus tumor necrosis factor receptor 1: a new neuroinflammatory piece of the complex Alzheimer\u2019s disease puzzle"],"prefix":"10.4103","volume":"14","author":[{"given":"Sophie","family":"Steeland","sequence":"first","affiliation":[{"name":"VIB Center for Inflammation Research, Ghent, Belgium"},{"name":"Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8327-620X","authenticated-orcid":false,"given":"Roosmarijn E.","family":"Vandenbroucke","sequence":"additional","affiliation":[{"name":"VIB Center for Inflammation Research, Ghent, Belgium"},{"name":"Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"R1-20260525","doi-asserted-by":"crossref","first-page":"534","DOI":"10.4103\/1673-5374.180372","article-title":"The choroid plexus-cerebrospinal fluid interface in Alzheimer\u2019s disease: more than just a barrier","volume":"11","author":"Balusu","year":"2016","journal-title":"Neural Regen 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neurodegeneration","volume":"353","author":"Ransohoff","year":"2016","journal-title":"Science"},{"key":"R9-20260525","doi-asserted-by":"crossref","first-page":"S18","DOI":"10.1038\/d41586-018-05724-7","article-title":"A quest to stave off the inevitable","volume":"559","author":"Sohn","year":"2018","journal-title":"Nature"},{"key":"R10-20260525","doi-asserted-by":"crossref","first-page":"E1442","DOI":"10.3390\/ijms19051442","article-title":"A new venue of TNF targeting","volume":"19","author":"Steeland","year":"2018","journal-title":"Int J Mol Sci"},{"key":"R11-20260525","doi-asserted-by":"crossref","first-page":"e8300","DOI":"10.15252\/emmm.201708300","article-title":"Counteracting the effects of TNF receptor-1 has therapeutic potential in Alzheimer\u2019s disease","volume":"10","author":"Steeland","year":"2018","journal-title":"EMBO Mol Med"},{"key":"R12-20260525","doi-asserted-by":"crossref","first-page":"713","DOI":"10.2165\/11310810-000000000-00000","article-title":"Tumour necrosis factor modulation for treatment of Alzheimer\u2019s disease: rationale and current evidence","volume":"23","author":"Tobinick","year":"2009","journal-title":"CNS Drugs"},{"key":"R13-20260525","doi-asserted-by":"crossref","first-page":"904","DOI":"10.1038\/nrd4390","article-title":"Is there new hope for therapeutic matrix metalloproteinase inhibition?","volume":"13","author":"Vandenbroucke","year":"2014","journal-title":"Nat Rev Drug Discov"}],"container-title":["Neural Regeneration Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ovid.com\/01300535-201914070-00007","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T19:28:44Z","timestamp":1786735724000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ovid.com\/10.4103\/1673-5374.247443"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,7]]},"references-count":13,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2019]]}},"URL":"https:\/\/doi.org\/10.4103\/1673-5374.247443","relation":{},"ISSN":["1673-5374","1876-7958"],"issn-type":[{"value":"1673-5374","type":"print"},{"value":"1876-7958","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,7]]},"assertion":[{"value":"2018-08-23","name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-10-24","name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}}]}}