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Whereas the pathology of these diseases is complex, chronic central inflammation, or neuroinflammation, is commonly observed across many neurodegenerative diseases. Despite a huge wealth of resources and promising preclinical testing, effective disease\u2010modifying therapies do not exist. This failure is owing to a combination of poor biological understanding of this response, unsuitable animal models, and poor scaling from pathway up to clinical levels. In order to address these challenges, systems\u2010level mathematical models may be utilized. Here, we provide a background on neuroinflammation and summarize available mathematical models of this response. Models described by ordinary, partial, and delay differential equations, and Boolean logic are introduced and discussed. The results as discussed in this review suggest logic\u2010based modeling as a formalism capable of managing the challenges associated with the modeling of CNS diseases.<\/jats:p>","DOI":"10.1002\/psp4.70064","type":"journal-article","created":{"date-parts":[[2025,8,13]],"date-time":"2025-08-13T12:13:09Z","timestamp":1755087189000},"page":"1908-1922","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Mathematical Modeling of Neuroinflammation in Neurodegenerative Diseases"],"prefix":"10.1002","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0708-8434","authenticated-orcid":false,"given":"Alex","family":"Foster\u2010Powell","sequence":"first","affiliation":[{"name":"CAPKR, University of Manchester  Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3917-844X","authenticated-orcid":false,"given":"Amin","family":"Rostami\u2010Hodjegan","sequence":"additional","affiliation":[{"name":"CAPKR, University of Manchester  Manchester UK"},{"name":"Certara, Predictive Technologies  Sheffield UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2631-3705","authenticated-orcid":false,"given":"Guy","family":"Meno\u2010Tetang","sequence":"additional","affiliation":[{"name":"Neuroscience R&amp;D, AstraZeneca  Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4848-0440","authenticated-orcid":false,"given":"Donald E.","family":"Mager","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences University at Buffalo, SUNY  Buffalo New York USA"},{"name":"Enhanced Pharmacodynamics, LLC  Buffalo New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2446-6895","authenticated-orcid":false,"given":"Kayode","family":"Ogungbenro","sequence":"additional","affiliation":[{"name":"CAPKR, University of Manchester  Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,8,13]]},"reference":[{"key":"e_1_2_8_2_1","unstructured":"United Nations Department of Economic and Social Affairs \u201cWorld Population Prospects 2019 Highlights \u201d(2019)."},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/trc2.12179"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd4164"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/psp4.12478"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10928-017-9567-4"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-191150"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2019.01008"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.02122"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40336-015-0147-6"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2020.00810"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1006\/nbdi.2002.0487"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(07)70270-3"},{"key":"e_1_2_8_14_1","unstructured":"P. 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