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@MISC{deWeerd:282944,
      author       = {deWeerd, Lis and Sandmann, T. and Ha, C. and Xia, D. and
                      Lewcock, JW and Monroe, KM and Haass, Christian},
      title        = {{D}ataset: {C}hronic {A}ducanumab-mediated clearance of
                      amyloid plaques decreases microglial activation and induces
                      a unique microglial phenotype associated with antigen
                      presentation},
      publisher    = {Gene Expression Omnibus},
      reportid     = {DZNE-2025-01405},
      year         = {2025},
      abstract     = {Anti-amyloid β-peptide (Aβ) immune therapy was developed
                      as treatment for Alzheimer’s disease (AD) to reduce and
                      prevent amyloid plaque pathology. This approach has proven
                      successful in phase 3 clinical trials of Aducanumab,
                      Lecanemab and Donanemab. These antibodies induce robust
                      amyloid plaque clearance, slow memory decline, and have
                      beneficial effects on daily living activities. The
                      therapeutic effects correlate with the efficacy of plaque
                      removal. Treatment is associated with adverse side-effects,
                      such as oedema and haemorrhages (ARIA-E and -H), which are
                      potentially linked to the induced immune response. To
                      improve therapeutic safety, it is therefore imperative to
                      understand the effects of anti-Aβ antibody treatment on
                      immune cell function. We investigated the effects of
                      long-term chronic Aducanumab treatment on amyloid plaque
                      pathology and microglial response in the APP-SAA triple
                      knock-in mouse model. Mice were treated weekly with
                      Aducanumab from 4-8 months of age. Long-term treatment with
                      Aducanumab results in a robust and dose-dependent removal of
                      amyloid plaque pathology. Analysis of the CSF proteome
                      indicates a reduction of markers for neurodegeneration
                      including tau and α-synuclein. Consistent with a reduction
                      of glucose uptake, the therapeutic effects were accompanied
                      by reduced microglial activation. RNAseq confirmed a
                      dose-dependent decrease in the disease-associated microglia
                      (DAM) transcriptional signature of microglia, which is
                      supported by a parallel decrease of Trem2 protein. However,
                      genes associated with antigen-presentation were still
                      increased after treatment. IHC confirms that Aducanumab
                      treatment increases microglial clustering, as well as MHC-II
                      expression around plaques and ELISA confirmed increased
                      cytokine levels. These findings demonstrate that long-term
                      chronic Aducanumab-mediated removal of Aβ leads to a dose
                      dependent decrease in microglial activation and
                      neurodegeneration, but induces a unique antibody
                      treatment-related microglial phenotype associated with
                      antigen presentation, which may be related to plaques still
                      present after the 4 months treatment period.},
      cin          = {AG Haass},
      cid          = {I:(DE-2719)1110007},
      pnm          = {352 - Disease Mechanisms (POF4-352)},
      pid          = {G:(DE-HGF)POF4-352},
      typ          = {PUB:(DE-HGF)32},
      url          = {https://pub.dzne.de/record/282944},
}