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@ARTICLE{Miller:272860,
      author       = {Miller, Stephanie R and Luxem, Kevin and Lauderdale, Kelli
                      and Nambiar, Pranav and Honma, Patrick S and Ly, Katie K and
                      Bangera, Shreya and Bullock, Mary and Shin, Jia and Kaliss,
                      Nick and Qiu, Yuechen and Cai, Catherine and Shen, Kevin and
                      Mallen, K Dakota and Yan, Zhaoqi and Mendiola, Andrew S and
                      Saito, Takashi and Saido, Takaomi C and Pico, Alexander R
                      and Thomas, Reuben and Roberson, Erik D and Akassoglou,
                      Katerina and Bauer, Pavol and Remy, Stefan and Palop, Jorge
                      J},
      title        = {{M}achine learning reveals prominent spontaneous behavioral
                      changes and treatment efficacy in humanized and transgenic
                      {A}lzheimer's disease models.},
      journal      = {Cell reports},
      volume       = {43},
      number       = {11},
      issn         = {2211-1247},
      address      = {[New York, NY]},
      publisher    = {Elsevier},
      reportid     = {DZNE-2024-01278},
      pages        = {114870},
      year         = {2024},
      abstract     = {Computer-vision and machine-learning (ML) approaches are
                      being developed to provide scalable, unbiased, and sensitive
                      methods to assess mouse behavior. Here, we used the ML-based
                      variational animal motion embedding (VAME) segmentation
                      platform to assess spontaneous behavior in humanized App
                      knockin and transgenic APP models of Alzheimer's disease
                      (AD) and to test the role of AD-related neuroinflammation in
                      these behavioral manifestations. We found marked alterations
                      in spontaneous behavior in AppNL-G-F and 5xFAD mice,
                      including age-dependent changes in motif utilization,
                      disorganized behavioral sequences, increased transitions,
                      and randomness. Notably, blocking fibrinogen-microglia
                      interactions in 5xFAD-Fggγ390-396A mice largely prevented
                      spontaneous behavioral alterations, indicating a key role
                      for neuroinflammation. Thus, AD-related spontaneous
                      behavioral alterations are prominent in knockin and
                      transgenic models and sensitive to therapeutic
                      interventions. VAME outcomes had higher specificity and
                      sensitivity than conventional behavioral outcomes. We
                      conclude that spontaneous behavior effectively captures age-
                      and sex-dependent disease manifestations and treatment
                      efficacy in AD models.},
      keywords     = {Alzheimer Disease: pathology / Alzheimer Disease: genetics
                      / Animals / Machine Learning / Humans / Mice, Transgenic /
                      Disease Models, Animal / Mice / Behavior, Animal / Male /
                      Female / Treatment Outcome / Amyloid beta-Protein Precursor:
                      genetics / Amyloid beta-Protein Precursor: metabolism /
                      Mice, Inbred C57BL / App-KI (Other) / CP: Neuroscience
                      (Other) / DeepLabCut (Other) / Keypoint-MoSeq (Other) /
                      amyloid (Other) / behavioral segmentation (Other) /
                      cognition (Other) / naturalistic behavior (Other) / open
                      field (Other) / pose estimation (Other) / preclinical
                      (Other)},
      cin          = {AG Remy},
      ddc          = {610},
      cid          = {I:(DE-2719)1013006},
      pnm          = {351 - Brain Function (POF4-351)},
      pid          = {G:(DE-HGF)POF4-351},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:39427315},
      doi          = {10.1016/j.celrep.2024.114870},
      url          = {https://pub.dzne.de/record/272860},
}