TY  - JOUR
AU  - Njavro, Jasenka
AU  - Vukicevic, Marija
AU  - Fiorini, Emma
AU  - Dinkel, Lina
AU  - Müller, Stephan A
AU  - Berghofer, Anna
AU  - Bordier, Chiara
AU  - Kozlov, Stanislav
AU  - Halle, Annett
AU  - Buschmann, Katrin
AU  - Capell, Anja
AU  - Giudici, Camilla
AU  - Willem, Michael
AU  - Feederle, Regina
AU  - Lichtenthaler, Stefan F
AU  - Babolin, Chiara
AU  - Montanari, Paolo
AU  - Pfeifer, Andrea
AU  - Kosco-Vilbois, Marie
AU  - Tahirovic, Sabina
TI  - Beneficial Effect of ACI-24 Vaccination on Aβ Plaque Pathology and Microglial Phenotypes in an Amyloidosis Mouse Model.
JO  - Cells
VL  - 12
IS  - 1
SN  - 2073-4409
CY  - Basel
PB  - MDPI
M1  - DZNE-2023-00136
SP  - 79
PY  - 2022
AB  - 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.
KW  - Mice
KW  - Animals
KW  - Microglia: metabolism
KW  - Amyloid beta-Protein Precursor: metabolism
KW  - Mice, Transgenic
KW  - Amyloid beta-Peptides: metabolism
KW  - Alzheimer Disease: genetics
KW  - Alzheimer Disease: therapy
KW  - Alzheimer Disease: metabolism
KW  - Amyloidosis: metabolism
KW  - Plaque, Amyloid: metabolism
KW  - Phenotype
KW  - Vaccination
KW  - Alzheimer’s disease (Other)
KW  - ACI-24 (Other)
KW  - Alzheimer’s disease (Other)
KW  - Aβ vaccine (Other)
KW  - immunotherapy (Other)
KW  - microglia (Other)
KW  - Amyloid beta-Protein Precursor (NLM Chemicals)
KW  - Amyloid beta-Peptides (NLM Chemicals)
KW  - Aβ vaccine (Other)
LB  - PUB:(DE-HGF)16
C6  - pmid:36611872
C2  - pmc:PMC9818422
DO  - DOI:10.3390/cells12010079
UR  - https://pub.dzne.de/record/169361
ER  -