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@ARTICLE{Kaji:275846,
      author       = {Kaji, Seiji and Berghoff, Stefan A and Spieth, Lena and
                      Schlaphoff, Lennart and Sasmita, Andrew O and Vitale, Simona
                      and Büschgens, Luca and Kedia, Shreeya and Zirngibl, Martin
                      and Nazarenko, Taisiia and Damkou, Alkmini and Hosang, Leon
                      and Depp, Constanze and Kamp, Frits and Scholz, Patricia and
                      Ewers, David and Giera, Martin and Ischebeck, Till and
                      Wurst, Wolfgang and Wefers, Benedikt and Schifferer, Martina
                      and Willem, Michael and Nave, Klaus-Armin and Haass,
                      Christian and Arzberger, Thomas and Jäkel, Sarah and
                      Wirths, Oliver and Saher, Gesine and Simons, Mikael},
      title        = {{A}polipoprotein {E} aggregation in microglia initiates
                      {A}lzheimer's disease pathology by seeding β-amyloidosis.},
      journal      = {Immunity},
      volume       = {57},
      number       = {11},
      issn         = {1074-7613},
      address      = {[Cambridge, Mass.]},
      publisher    = {Cell Press},
      reportid     = {DZNE-2025-00081},
      pages        = {2651 - 2668.e12},
      year         = {2024},
      abstract     = {The seeded growth of pathogenic protein aggregates
                      underlies the pathogenesis of Alzheimer's disease (AD), but
                      how this pathological cascade is initiated is not fully
                      understood. Sporadic AD is linked genetically to
                      apolipoprotein E (APOE) and other genes expressed in
                      microglia related to immune, lipid, and endocytic functions.
                      We generated a transgenic knockin mouse expressing
                      HaloTag-tagged APOE and optimized experimental protocols for
                      the biochemical purification of APOE, which enabled us to
                      identify fibrillary aggregates of APOE in mice with
                      amyloid-β (Aβ) amyloidosis and in human AD brain
                      autopsies. These APOE aggregates that stained positive for
                      β sheet-binding dyes triggered Aβ amyloidosis within the
                      endo-lysosomal system of microglia, in a process influenced
                      by microglial lipid metabolism and the JAK/STAT signaling
                      pathway. Taking these observations together, we propose a
                      model for the onset of Aβ amyloidosis in AD, suggesting
                      that the endocytic uptake and aggregation of APOE by
                      microglia can initiate Aβ plaque formation.},
      keywords     = {Animals / Alzheimer Disease: metabolism / Alzheimer
                      Disease: pathology / Microglia: metabolism / Mice / Humans /
                      Mice, Transgenic / Amyloid beta-Peptides: metabolism /
                      Amyloidosis: metabolism / Amyloidosis: pathology /
                      Amyloidosis: genetics / Apolipoproteins E: metabolism /
                      Apolipoproteins E: genetics / Signal Transduction / Plaque,
                      Amyloid: metabolism / Plaque, Amyloid: pathology / Brain:
                      metabolism / Brain: pathology / Disease Models, Animal /
                      Lipid Metabolism / Protein Aggregation, Pathological / STAT
                      Transcription Factors: metabolism / Janus Kinases:
                      metabolism / Alzheimer’s disease (Other) / ApoE (Other) /
                      inflammation (Other) / lipids (Other) / microglia (Other) /
                      Amyloid beta-Peptides (NLM Chemicals) / Apolipoproteins E
                      (NLM Chemicals) / STAT Transcription Factors (NLM Chemicals)
                      / Janus Kinases (NLM Chemicals)},
      cin          = {AG Simons / AG Wurst / AG Misgeld / AG Haass},
      ddc          = {610},
      cid          = {I:(DE-2719)1110008 / I:(DE-2719)1140001 /
                      I:(DE-2719)1110000-4 / I:(DE-2719)1110007},
      pnm          = {351 - Brain Function (POF4-351) / 352 - Disease Mechanisms
                      (POF4-352)},
      pid          = {G:(DE-HGF)POF4-351 / G:(DE-HGF)POF4-352},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:39419029},
      doi          = {10.1016/j.immuni.2024.09.014},
      url          = {https://pub.dzne.de/record/275846},
}