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Rudan Njavro, J.* ; Vukicevic, M.* ; Fiorini, E.* ; Dinkel, L.* ; Müller, S.A.* ; Berghofer, A.* ; Bordier, C.* ; Kozlov, S.* ; Halle, A.* ; Buschmann, K.* ; Capell, A.* ; Giudici, C.* ; Willem, M.* ; Feederle, R. ; Lichtenthaler, S.F.* ; Babolin, C.* ; Montanari, P.* ; Pfeifer, A.* ; Kosco-Vilbois, M.* ; Tahirovic, S.*

Beneficial effect of ACI-24 vaccination on Aβ plaque pathology and microglial phenotypes in an amyloidosis mouse model.

Cells 12:79 (2023)
Verlagsversion Forschungsdaten DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
Amyloid-β (Aβ) deposition is an initiating factor in Alzheimer's disease (AD). Microglia are the brain immune cells that surround and phagocytose Aβ 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 Aβ 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 Aβ plaque load, Aβ 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 Aβ plaques, we observed a more ramified morphology of Aβ 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 Aβ plaque load triggered by ACI-24 vaccination. Our study demonstrates that administration of the Aβ targeting vaccine ACI-24 reduces AD pathology, suggesting its use as a safe and cost-effective AD therapeutic intervention.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Aci-24 ; Alzheimer’s Disease ; Aβ Vaccine ; Immunotherapy ; Microglia; Alzheimers-disease; Clearance; Mice; Immunization; Trials; Meningoencephalitis; Hypothesis; Deposition; Antibodies; Toxicity
ISSN (print) / ISBN 2073-4409
e-ISSN 2073-4409
Zeitschrift Cells
Quellenangaben Band: 12, Heft: 1, Seiten: , Artikelnummer: 79 Supplement: ,
Verlag MDPI
Verlagsort Basel
Nichtpatentliteratur Publikationen
Institut(e) CF Monoclonal Antibodies (CF-MAB)
Förderungen Bundesministerium für Bildung und Forschung
Deutsche Forschungsgemeinschaft
Alzheimer Forschung Initiative
AC Immune SA