{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T15:56:37Z","timestamp":1790006197310,"version":"4.0.1"},"reference-count":163,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2024,1,9]],"date-time":"2024-01-09T00:00:00Z","timestamp":1704758400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIH\/NIA","award":["RF1 AG060057"],"award-info":[{"award-number":["RF1 AG060057"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>As an essential component of our innate immune system, the complement system is responsible for our defense against pathogens. The complement cascade has complex roles in the central nervous system (CNS), most of what we know about it stems from its role in brain development. However, in recent years, numerous reports have implicated the classical complement cascade in both brain development and decline. More specifically, complement dysfunction has been implicated in neurodegenerative disorders, such as Alzheimer\u2019s disease (AD), which is the most common form of dementia. Synapse loss is one of the main pathological hallmarks of AD and correlates with memory impairment. Throughout the course of AD progression, synapses are tagged with complement proteins and are consequently removed by microglia that express complement receptors. Notably, astrocytes are also capable of secreting signals that induce the expression of complement proteins in the CNS. Both astrocytes and microglia are implicated in neuroinflammation, another hallmark of AD pathogenesis. In this review, we provide an overview of previously known and newly established roles for the complement cascade in the CNS and we explore how complement interactions with microglia, astrocytes, and other risk factors such as TREM2 and ApoE4 modulate the processes of neurodegeneration in both amyloid and tau models of AD.<\/jats:p>","DOI":"10.3390\/ijms25020817","type":"journal-article","created":{"date-parts":[[2024,1,9]],"date-time":"2024-01-09T04:38:51Z","timestamp":1704775131000},"page":"817","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":70,"title":["The Importance of Complement-Mediated Immune Signaling in Alzheimer\u2019s Disease Pathogenesis"],"prefix":"10.3390","volume":"25","author":[{"given":"Andr\u00e9 F.","family":"Batista","sequence":"first","affiliation":[{"name":"Ann Romney Center for Neurologic Diseases, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khyrul A.","family":"Khan","sequence":"additional","affiliation":[{"name":"Ann Romney Center for Neurologic Diseases, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria-Tzousi","family":"Papavergi","sequence":"additional","affiliation":[{"name":"Ann Romney Center for Neurologic Diseases, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, MA 02115, USA"},{"name":"School for Mental Health and Neuroscience (MHeNs), Department of Psychiatry and Neuropsychology, Maastricht University, P.O. Box 616, 6200 MD Maastricht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2983-7870","authenticated-orcid":false,"given":"Cynthia A.","family":"Lemere","sequence":"additional","affiliation":[{"name":"Ann Romney Center for Neurologic Diseases, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,1,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"595","DOI":"10.15252\/emmm.201606210","article-title":"The amyloid hypothesis of Alzheimer\u2019s disease at 25 years","volume":"8","author":"Selkoe","year":"2016","journal-title":"EMBO Mol. Med."},{"key":"ref_2","unstructured":"Alzheimer\u2019s Disease, International, and Patterson, C. (2018). 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