Home > Publications Database > Beneficial Effect of ACI-24 Vaccination on Aβ Plaque Pathology and Microglial Phenotypes in an Amyloidosis Mouse Model. > print

001     169361
005     20240112171833.0
024 7 _ |a 10.3390/cells12010079
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024 7 _ |a pmc:PMC9818422
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037 _ _ |a DZNE-2023-00136
041 _ _ |a English
082 _ _ |a 570
100 1 _ |a Njavro, Jasenka
|0 P:(DE-2719)2811277
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|e First author
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245 _ _ |a Beneficial Effect of ACI-24 Vaccination on Aβ Plaque Pathology and Microglial Phenotypes in an Amyloidosis Mouse Model.
260 _ _ |a Basel
|c 2022
|b MDPI
336 7 _ |a article
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336 7 _ |a Journal Article
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|s 1673873794_16648
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336 7 _ |a ARTICLE
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336 7 _ |a Journal Article
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520 _ _ |a 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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650 _ 2 |a Mice
|2 MeSH
650 _ 2 |a Animals
|2 MeSH
650 _ 2 |a Microglia: metabolism
|2 MeSH
650 _ 2 |a Amyloid beta-Protein Precursor: metabolism
|2 MeSH
650 _ 2 |a Mice, Transgenic
|2 MeSH
650 _ 2 |a Amyloid beta-Peptides: metabolism
|2 MeSH
650 _ 2 |a Alzheimer Disease: genetics
|2 MeSH
650 _ 2 |a Alzheimer Disease: therapy
|2 MeSH
650 _ 2 |a Alzheimer Disease: metabolism
|2 MeSH
650 _ 2 |a Amyloidosis: metabolism
|2 MeSH
650 _ 2 |a Plaque, Amyloid: metabolism
|2 MeSH
650 _ 2 |a Phenotype
|2 MeSH
650 _ 2 |a Vaccination
|2 MeSH
650 _ 7 |a Alzheimer’s disease
|2 Other
650 _ 7 |a ACI-24
|2 Other
650 _ 7 |a Alzheimer’s disease
|2 Other
650 _ 7 |a Aβ vaccine
|2 Other
650 _ 7 |a immunotherapy
|2 Other
650 _ 7 |a microglia
|2 Other
650 _ 7 |a Amyloid beta-Protein Precursor
|2 NLM Chemicals
650 _ 7 |a Amyloid beta-Peptides
|2 NLM Chemicals
650 _ 7 |a Aβ vaccine
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700 1 _ |a Vukicevic, Marija
|b 1
700 1 _ |a Fiorini, Emma
|b 2
700 1 _ |a Dinkel, Lina
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700 1 _ |a Müller, Stephan A
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700 1 _ |a Berghofer, Anna
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700 1 _ |a Bordier, Chiara
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700 1 _ |a Kozlov, Stanislav
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700 1 _ |a Halle, Annett
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700 1 _ |a Buschmann, Katrin
|0 P:(DE-2719)9002284
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700 1 _ |a Capell, Anja
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700 1 _ |a Giudici, Camilla
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700 1 _ |a Willem, Michael
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700 1 _ |a Feederle, Regina
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700 1 _ |a Lichtenthaler, Stefan F
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700 1 _ |a Babolin, Chiara
|b 15
700 1 _ |a Montanari, Paolo
|b 16
700 1 _ |a Pfeifer, Andrea
|b 17
700 1 _ |a Kosco-Vilbois, Marie
|b 18
700 1 _ |a Tahirovic, Sabina
|0 P:(DE-2719)2442036
|b 19
|e Last author
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773 _ _ |a 10.3390/cells12010079
|g Vol. 12, no. 1, p. 79 -
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|t Cells
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