{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T15:13:56Z","timestamp":1790954036464,"version":"4.1.0"},"reference-count":61,"publisher":"SAGE Publications","issue":"3","license":[{"start":{"date-parts":[[2021,2,2]],"date-time":"2021-02-02T00:00:00Z","timestamp":1612224000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Alzheimer\u2019s Disease"],"published-print":{"date-parts":[[2021,2,2]]},"abstract":"<jats:p>Microglia constitute the brain\u2019s immune system and their involvement in Alzheimer\u2019s disease has been discussed. Commonly, and in line with the amyloid\/neuroinflammation cascade hypothesis, microglia have been portrayed as potentially dangerous immune effector cells thought to be overactivated by amyloid and producing neurotoxic inflammatory mediators that lead to neurofibrillary degeneration. We disagree with this theory and offer as an alternative the microglial dysfunction theory stating that microglia become impaired in their normally neuroprotective roles because of aging, i.e., they become senescent and aging neurons degenerate because they lack the needed microglial support for their survival. Thus, while the amyloid cascade theory relies primarily on genetic data, the dysfunction theory incorporates aging as a critical etiological factor. Aging is the greatest risk factor for the sporadic (late-onset) and most common form of Alzheimer\u2019s disease, where fully penetrant genetic mutations are absent. In this review, we lay out and discuss the human evidence that supports senescent microglial dysfunction and conflicts with the amyloid\/neuroinflammation idea.<\/jats:p>","DOI":"10.3233\/jad-201248","type":"journal-article","created":{"date-parts":[[2021,2,2]],"date-time":"2021-02-02T18:41:49Z","timestamp":1612291309000},"page":"961-968","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":73,"title":["The Role of Microglia in Sporadic Alzheimer\u2019s Disease"],"prefix":"10.1177","volume":"79","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4973-9052","authenticated-orcid":false,"given":"Wolfgang J.","family":"Streit","sequence":"first","affiliation":[{"name":"Department of Neuroscience, University of Florida, Gainesville, FL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Habibeh","family":"Khoshbouei","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, University of Florida, Gainesville, FL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ingo","family":"Bechmann","sequence":"additional","affiliation":[{"name":"Anatomical Institute, University of Leipzig, Leipzig, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2025,2,5]]},"reference":[{"key":"ref001","doi-asserted-by":"publisher","DOI":"10.1038\/s41583-019-0201-x"},{"key":"ref002","doi-asserted-by":"publisher","DOI":"10.1002\/glia.10154"},{"key":"ref003","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.20093"},{"key":"ref004","doi-asserted-by":"publisher","DOI":"10.1002\/glia.10319"},{"key":"ref005","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-009-0556-6"},{"key":"ref006","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2013.579"},{"key":"ref007","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1211103"},{"key":"ref008","doi-asserted-by":"publisher","DOI":"10.1002\/glia.20710"},{"key":"ref009","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2020.104962"},{"key":"ref010","doi-asserted-by":"publisher","DOI":"10.1016\/S0197-4580(01)00289-5"},{"key":"ref011","doi-asserted-by":"publisher","DOI":"10.1002\/glia.10146"},{"key":"ref012","doi-asserted-by":"publisher","DOI":"10.1126\/science.1092864"},{"key":"ref013","doi-asserted-by":"publisher","DOI":"10.1016\/S0197-4580(01)00287-1"},{"key":"ref014","doi-asserted-by":"publisher","DOI":"10.1111\/j.1474-9728.2004.00101.x"},{"key":"ref015","first-page":"22","volume":"2","author":"Streit WJ","year":"2010","journal-title":"Front Aging Neurosci"},{"key":"ref016","doi-asserted-by":"publisher","DOI":"10.1126\/science.1566067"},{"key":"ref017","doi-asserted-by":"publisher","DOI":"10.1002\/path.2885"},{"key":"ref018","doi-asserted-by":"publisher","DOI":"10.1097\/NEN.0b013e318232a379"},{"key":"ref019","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-319-12679-1_1"},{"key":"ref020","doi-asserted-by":"publisher","DOI":"10.1097\/00005072-197705000-00006"},{"key":"ref021","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-016-1562-0"},{"key":"ref022","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3940(87)90696-3"},{"key":"ref023","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.57.6.831"},{"key":"ref024","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.2008.65.7.nct70006"},{"key":"ref025","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2010.12.014"},{"key":"ref026","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2015.10.012"},{"key":"ref027","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.2001.00216.x"},{"key":"ref028","doi-asserted-by":"publisher","DOI":"10.1002\/glia.23510"},{"key":"ref029","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awv236"},{"key":"ref030","doi-asserted-by":"publisher","DOI":"10.1016\/S0197-4580(97)00056-0"},{"key":"ref031","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2013.00050"},{"key":"ref032","doi-asserted-by":"publisher","DOI":"10.1016\/0197-4580(91)90006-6"},{"key":"ref033","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-010-0789-4"},{"key":"ref034","doi-asserted-by":"crossref","unstructured":"AlzheimerA (1911) Ueber eigenartigeKrankheitsfaelle des spaeteren Alters\n                      Zeitschr. 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