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Among the autoantibodies most frequently associated with manifestations mimicking neurodegenerative disorders\u2014such as dementia, parkinsonism, ataxia and motor neuron disease\u2014IgLON5-, LGI1- and CASPR2-antibodies, predominantly of the IgG4 subclass and associated with specific HLA haplotypes, are the most common. Since these forms of autoimmune encephalitis often lack inflammatory findings in cerebrospinal fluid or magnetic resonance imaging, recognizing clinical \u2018red flags\u2019 suggestive of an autoimmune etiology is crucial for accurate diagnosis and timely initiation of immunotherapy. Interestingly, in these forms of autoimmune encephalitis, both inflammatory and neurodegenerative disease mechanisms may be involved. The neurodegenerative component may result directly from antibody effects (e.g., tau deposition in IgLON5-antibody disease) or arise through other mechanisms (e.g., seizures or exacerbation of pre-existing pathology). Moreover, neuroinflammation has recently emerged as a key contributor to primary neurodegenerative disorders. For instance, microglial activation promotes tau pathology propagation, as observed in Alzheimer\u2019s disease and other primary neurodegenerative disorders. While the precise mechanisms linking inflammation and neurodegeneration remain to be fully understood, further research into the interplay between autoimmunity and neurodegeneration may enhance our understanding of disease mechanisms and expand therapeutic opportunities in both autoimmune and neurodegenerative neurological disorders.<\/jats:p>","DOI":"10.1007\/s00415-025-13094-0","type":"journal-article","created":{"date-parts":[[2025,4,24]],"date-time":"2025-04-24T14:07:47Z","timestamp":1745503667000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Neurodegeneration and the immune system: lessons from autoimmune encephalitis"],"prefix":"10.1007","volume":"272","author":[{"given":"Lucia","family":"Campetella","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krzysztof","family":"Smolik","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Farina","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bastien","family":"Joubert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergio","family":"Mu\u00f1iz-Castrillo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Virginie","family":"Desestret","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4721-5952","authenticated-orcid":false,"given":"J\u00e9r\u00f4me","family":"Honnorat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,4,24]]},"reference":[{"issue":"2","key":"13094_CR1","doi-asserted-by":"publisher","first-page":"839","DOI":"10.1152\/physrev.00010.2016","volume":"97","author":"J Dalmau","year":"2017","unstructured":"Dalmau J, Geis C, Graus F (2017) Autoantibodies to synaptic receptors and neuronal cell surface proteins in autoimmune diseases of the central nervous system. 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