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Most clinical trials targeting the classical hallmarks of this disease\u2014\u03b2-amyloid plaques and neurofibrillary tangles\u2014failed, showed discrete clinical effects, or were accompanied by concerning side effects. There has been an ongoing search for novel therapeutic targets. Neuroinflammation, now widely recognized as a hallmark of all neurodegenerative diseases, has been proven to be a major contributor to AD pathology. Here, we summarize the role of neuroinflammation in the pathogenesis and progression of AD and discuss potential targets such as microglia, TREM2, the complement system, inflammasomes, and cytosolic DNA sensors. We also present an overview of ongoing studies targeting specific innate immune system components, highlighting the progress in this field of drug research while bringing attention to the delicate nature of innate immune modulations in AD.<\/jats:p>","DOI":"10.3390\/cells13171426","type":"journal-article","created":{"date-parts":[[2024,8,26]],"date-time":"2024-08-26T04:48:25Z","timestamp":1724647705000},"page":"1426","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Therapeutic Targets in Innate Immunity to Tackle Alzheimer\u2019s Disease"],"prefix":"10.3390","volume":"13","author":[{"given":"Maria L.","family":"Serradas","sequence":"first","affiliation":[{"name":"Institute of Physiology II, University Hospital Bonn, 53115 Bonn, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingying","family":"Ding","sequence":"additional","affiliation":[{"name":"Institute of Physiology II, University Hospital Bonn, 53115 Bonn, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paula V.","family":"Martorell","sequence":"additional","affiliation":[{"name":"Institute of Clinical Chemistry and Clinical Pharmacology, University Hospital Bonn, 53127 Bonn, Germany"},{"name":"German Center for Neurodegenerative Diseases (DZNE), 53127 Bonn, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ida","family":"Kuli\u0144ska","sequence":"additional","affiliation":[{"name":"Institute of Physiology II, University Hospital Bonn, 53115 Bonn, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1581-474X","authenticated-orcid":false,"given":"Sergio","family":"Castro-Gomez","sequence":"additional","affiliation":[{"name":"Institute of Physiology II, University Hospital Bonn, 53115 Bonn, Germany"},{"name":"Center for Neurology, Department of Parkinson, Sleep and Movement Disorders, University Hospital Bonn, 53127 Bonn, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,8,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Li, X., Feng, X., Sun, X., Hou, N., Han, F., and Liu, Y. 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