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@ARTICLE{Njavro:169361,
      author       = {Njavro, Jasenka and Vukicevic, Marija and Fiorini, Emma and
                      Dinkel, Lina and Müller, Stephan A and Berghofer, Anna and
                      Bordier, Chiara and Kozlov, Stanislav and Halle, Annett and
                      Buschmann, Katrin and Capell, Anja and Giudici, Camilla and
                      Willem, Michael and Feederle, Regina and Lichtenthaler,
                      Stefan F and Babolin, Chiara and Montanari, Paolo and
                      Pfeifer, Andrea and Kosco-Vilbois, Marie and Tahirovic,
                      Sabina},
      title        = {{B}eneficial {E}ffect of {ACI}-24 {V}accination on {A}β
                      {P}laque {P}athology and {M}icroglial {P}henotypes in an
                      {A}myloidosis {M}ouse {M}odel.},
      journal      = {Cells},
      volume       = {12},
      number       = {1},
      issn         = {2073-4409},
      address      = {Basel},
      publisher    = {MDPI},
      reportid     = {DZNE-2023-00136},
      pages        = {79},
      year         = {2022},
      abstract     = {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.},
      keywords     = {Mice / Animals / Microglia: metabolism / Amyloid
                      beta-Protein Precursor: metabolism / Mice, Transgenic /
                      Amyloid beta-Peptides: metabolism / Alzheimer Disease:
                      genetics / Alzheimer Disease: therapy / Alzheimer Disease:
                      metabolism / Amyloidosis: metabolism / Plaque, Amyloid:
                      metabolism / Phenotype / Vaccination / Alzheimer’s disease
                      (Other) / ACI-24 (Other) / Alzheimer’s disease (Other) /
                      Aβ vaccine (Other) / immunotherapy (Other) / microglia
                      (Other) / Amyloid beta-Protein Precursor (NLM Chemicals) /
                      Amyloid beta-Peptides (NLM Chemicals) / Aβ vaccine (Other)},
      cin          = {AG Tahirovic / AG Lichtenthaler / AG Halle / AG Haass old},
      ddc          = {570},
      cid          = {I:(DE-2719)1140003 / I:(DE-2719)1110006 /
                      I:(DE-2719)1013034 / I:(DE-2719)1110007},
      pnm          = {352 - Disease Mechanisms (POF4-352)},
      pid          = {G:(DE-HGF)POF4-352},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:36611872},
      pmc          = {pmc:PMC9818422},
      doi          = {10.3390/cells12010079},
      url          = {https://pub.dzne.de/record/169361},
}