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@ARTICLE{Schneeberger:278026,
      author       = {Schneeberger, Shirin and Kim, Seung Joon and Geesdorf,
                      Maria N and Friebel, Ekaterina and Eede, Pascale and
                      Jendrach, Marina and Boltengagen, Anastasiya and Braeuning,
                      Caroline and Ruhwedel, Torben and Hülsmeier, Andreas J and
                      Gimber, Niclas and Foerster, Marlene and Obst, Juliane and
                      Andreadou, Myrto and Mundt, Sarah and Schmoranzer, Jan and
                      Prokop, Stefan and Kessler, Wiebke and Kuhlmann, Tanja and
                      Möbius, Wiebke and Nave, Klaus-Armin and Hornemann,
                      Thorsten and Becher, Burkhard and Edgar, Julia M and
                      Karaiskos, Nikos and Kocks, Christine and Rajewsky, Nikolaus
                      and Heppner, Frank L},
      title        = {{I}nterleukin-12 signaling drives {A}lzheimer's disease
                      pathology through disrupting neuronal and oligodendrocyte
                      homeostasis.},
      journal      = {Nature aging},
      volume       = {5},
      number       = {4},
      issn         = {2662-8465},
      address      = {London},
      publisher    = {Nature Research},
      reportid     = {DZNE-2025-00536},
      pages        = {622 - 641},
      year         = {2025},
      abstract     = {Neuroinflammation including interleukin
                      (IL)-12/IL-23-signaling is central to Alzheimer's disease
                      (AD) pathology. Inhibition of p40, a subunit of IL-12/IL-23,
                      attenuates pathology in AD-like mice; however, its signaling
                      mechanism and expression pattern remained elusive. Here we
                      show that IL-12 receptors are predominantly expressed in
                      neurons and oligodendrocytes in AD-like APPPS1 mice and in
                      patients with AD, whereas IL-23 receptor transcripts are
                      barely detectable. Consistently, deletion of the IL-12
                      receptor in neuroectodermal cells ameliorated AD pathology
                      in APPPS1 mice, whereas removal of IL-23 receptors had no
                      effect. Genetic ablation of IL-12 signaling alone reverted
                      the loss of mature oligodendrocytes, restored myelin
                      homeostasis, rescued the amyloid-β-dependent reduction of
                      parvalbumin-positive interneurons and restored
                      phagocytosis-related changes in microglia of APPPS1 mice.
                      Furthermore, IL-12 protein expression was increased in human
                      AD brains compared to healthy age-matched controls, and
                      human oligodendrocyte-like cells responded profoundly to
                      IL-12 stimulation. We conclude that oligodendroglial and
                      neuronal IL-12 signaling, but not IL-23 signaling, are key
                      in orchestrating AD-related neuroimmune crosstalk and that
                      IL-12 represents an attractive therapeutic target in AD.},
      keywords     = {Alzheimer Disease: pathology / Alzheimer Disease:
                      metabolism / Alzheimer Disease: immunology / Alzheimer
                      Disease: genetics / Animals / Humans / Signal Transduction /
                      Mice / Oligodendroglia: metabolism / Oligodendroglia:
                      pathology / Homeostasis / Neurons: metabolism / Neurons:
                      pathology / Interleukin-12: metabolism / Interleukin-12:
                      genetics / Mice, Transgenic / Male / Receptors,
                      Interleukin-12: metabolism / Receptors, Interleukin-12:
                      genetics / Brain: pathology / Brain: metabolism / Disease
                      Models, Animal / Female / Microglia: metabolism / Aged /
                      Amyloid beta-Peptides: metabolism / Receptors, Interleukin:
                      metabolism / Receptors, Interleukin: genetics / Amyloid
                      beta-Protein Precursor: genetics / Interleukin-12 (NLM
                      Chemicals) / Receptors, Interleukin-12 (NLM Chemicals) /
                      Amyloid beta-Peptides (NLM Chemicals) / Receptors,
                      Interleukin (NLM Chemicals) / Amyloid beta-Protein Precursor
                      (NLM Chemicals)},
      cin          = {AG Heppner},
      ddc          = {610},
      cid          = {I:(DE-2719)1810007},
      pnm          = {353 - Clinical and Health Care Research (POF4-353)},
      pid          = {G:(DE-HGF)POF4-353},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:40082619},
      doi          = {10.1038/s43587-025-00816-2},
      url          = {https://pub.dzne.de/record/278026},
}