{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,25]],"date-time":"2026-07-25T09:12:59Z","timestamp":1784970779715,"version":"3.55.0"},"reference-count":69,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2022,12,24]],"date-time":"2022-12-24T00:00:00Z","timestamp":1671840000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010146","name":"Alzheimer Forschung Initiative","doi-asserted-by":"publisher","award":["18014"],"award-info":[{"award-number":["18014"]}],"id":[{"id":"10.13039\/100010146","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010146","name":"Alzheimer Forschung Initiative","doi-asserted-by":"publisher","award":["390857198"],"award-info":[{"award-number":["390857198"]}],"id":[{"id":"10.13039\/100010146","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010146","name":"Alzheimer Forschung Initiative","doi-asserted-by":"publisher","award":["JPND PMD-AD"],"award-info":[{"award-number":["JPND PMD-AD"]}],"id":[{"id":"10.13039\/100010146","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Deutsche Forschungsgemeinschaft (DFG, German Research Foundation)","award":["18014"],"award-info":[{"award-number":["18014"]}]},{"name":"Deutsche Forschungsgemeinschaft (DFG, German Research Foundation)","award":["390857198"],"award-info":[{"award-number":["390857198"]}]},{"name":"Deutsche Forschungsgemeinschaft (DFG, German Research Foundation)","award":["JPND PMD-AD"],"award-info":[{"award-number":["JPND PMD-AD"]}]},{"name":"Federal Ministry of Education and Research","award":["18014"],"award-info":[{"award-number":["18014"]}]},{"name":"Federal Ministry of Education and Research","award":["390857198"],"award-info":[{"award-number":["390857198"]}]},{"name":"Federal Ministry of Education and Research","award":["JPND PMD-AD"],"award-info":[{"award-number":["JPND PMD-AD"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Amyloid-\u03b2 (A\u03b2) deposition is an initiating factor in Alzheimer\u2019s disease (AD). Microglia are the brain immune cells that surround and phagocytose A\u03b2 plaques, but their phagocytic capacity declines in AD. This is in agreement with studies that associate AD risk loci with genes regulating the phagocytic function of immune cells. Immunotherapies are currently pursued as strategies against AD and there are increased efforts to understand the role of the immune system in ameliorating AD pathology. Here, we evaluated the effect of the A\u03b2 targeting ACI-24 vaccine in reducing AD pathology in an amyloidosis mouse model. ACI-24 vaccination elicited a robust and sustained antibody response in APPPS1 mice with an accompanying reduction of A\u03b2 plaque load, A\u03b2 plaque-associated ApoE and dystrophic neurites as compared to non-vaccinated controls. Furthermore, an increased number of NLRP3-positive plaque-associated microglia was observed following ACI-24 vaccination. In contrast to this local microglial activation at A\u03b2 plaques, we observed a more ramified morphology of A\u03b2 plaque-distant microglia compared to non-vaccinated controls. Accordingly, bulk transcriptomic analysis revealed a trend towards the reduced expression of several disease-associated microglia (DAM) signatures that is in line with the reduced A\u03b2 plaque load triggered by ACI-24 vaccination. Our study demonstrates that administration of the A\u03b2 targeting vaccine ACI-24 reduces AD pathology, suggesting its use as a safe and cost-effective AD therapeutic intervention.<\/jats:p>","DOI":"10.3390\/cells12010079","type":"journal-article","created":{"date-parts":[[2022,12,27]],"date-time":"2022-12-27T07:30:06Z","timestamp":1672126206000},"page":"79","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Beneficial Effect of ACI-24 Vaccination on A\u03b2 Plaque Pathology and Microglial Phenotypes in an Amyloidosis Mouse Model"],"prefix":"10.3390","volume":"12","author":[{"given":"Jasenka","family":"Rudan Njavro","sequence":"first","affiliation":[{"name":"German Center for Neurodegenerative Diseases (DZNE), 81377 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marija","family":"Vukicevic","sequence":"additional","affiliation":[{"name":"AC Immune SA, 1015 Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma","family":"Fiorini","sequence":"additional","affiliation":[{"name":"AC Immune SA, 1015 Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lina","family":"Dinkel","sequence":"additional","affiliation":[{"name":"German Center for Neurodegenerative Diseases (DZNE), 81377 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephan A.","family":"M\u00fcller","sequence":"additional","affiliation":[{"name":"German Center for Neurodegenerative Diseases (DZNE), 81377 Munich, Germany"},{"name":"Neuroproteomics, School of Medicine, Klinikum rechts der Isar, Technical University of Munich, 80333 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Berghofer","sequence":"additional","affiliation":[{"name":"Neuroproteomics, School of Medicine, Klinikum rechts der Isar, Technical University of Munich, 80333 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara","family":"Bordier","sequence":"additional","affiliation":[{"name":"German Center for Neurodegenerative Diseases (DZNE), 81377 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7160-7067","authenticated-orcid":false,"given":"Stanislav","family":"Kozlov","sequence":"additional","affiliation":[{"name":"German Center for Neurodegenerative Diseases (DZNE), 53127 Bonn, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annett","family":"Halle","sequence":"additional","affiliation":[{"name":"German Center for Neurodegenerative Diseases (DZNE), 53127 Bonn, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katrin","family":"Buschmann","sequence":"additional","affiliation":[{"name":"Biomedical Center (BMC), Ludwig-Maximilians University Munich, 80539 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anja","family":"Capell","sequence":"additional","affiliation":[{"name":"Biomedical Center (BMC), Ludwig-Maximilians University Munich, 80539 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camilla","family":"Giudici","sequence":"additional","affiliation":[{"name":"German Center for Neurodegenerative Diseases (DZNE), 81377 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Willem","sequence":"additional","affiliation":[{"name":"Biomedical Center (BMC), Ludwig-Maximilians University Munich, 80539 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3981-367X","authenticated-orcid":false,"given":"Regina","family":"Feederle","sequence":"additional","affiliation":[{"name":"German Center for Neurodegenerative Diseases (DZNE), 81377 Munich, Germany"},{"name":"Monoclonal Antibody Core Facility, Helmholtz Zentrum M\u00fcnchen, German Research Center for Environmental Health (GmbH), 85764 Neuherberg, Germany"},{"name":"Munich Cluster for Systems Neurology (SyNergy), 81377 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2211-2575","authenticated-orcid":false,"given":"Stefan F.","family":"Lichtenthaler","sequence":"additional","affiliation":[{"name":"German Center for Neurodegenerative Diseases (DZNE), 81377 Munich, Germany"},{"name":"Neuroproteomics, School of Medicine, Klinikum rechts der Isar, Technical University of Munich, 80333 Munich, Germany"},{"name":"Munich Cluster for Systems Neurology (SyNergy), 81377 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara","family":"Babolin","sequence":"additional","affiliation":[{"name":"AC Immune SA, 1015 Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo","family":"Montanari","sequence":"additional","affiliation":[{"name":"AC Immune SA, 1015 Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Pfeifer","sequence":"additional","affiliation":[{"name":"AC Immune SA, 1015 Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie","family":"Kosco-Vilbois","sequence":"additional","affiliation":[{"name":"AC Immune SA, 1015 Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4403-9559","authenticated-orcid":false,"given":"Sabina","family":"Tahirovic","sequence":"additional","affiliation":[{"name":"German Center for Neurodegenerative Diseases (DZNE), 81377 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1126\/science.1566067","article-title":"Alzheimer\u2019s Disease: The amyloid cascade hypothesis","volume":"256","author":"Hardy","year":"1992","journal-title":"Science"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1126\/science.1072994","article-title":"The amyloid hypothesis of Alzheimer\u2019s Disease: Progress and problems on the road to therapeutics","volume":"297","author":"Hardy","year":"2002","journal-title":"Science"},{"key":"ref_3","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. 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