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@ARTICLE{Meyer:280284,
      author       = {Meyer, Carolin and Niedermeier, Theresa and Feyen, Paul L C
                      and Strübing, Felix L and Rauchmann, Boris Stephan and
                      Karali, Katerina and Gentz, Johanna and Tillmann, Yannik and
                      Landgraf, Nicolas Friedrich and Rumpf, Svenja-Lotta and
                      Ochs, Katharina and Wind-Mark, Karin and Biechele, Gloria
                      and Wagner, Jessica and Guersel, Selim and Kurz, Carolin and
                      Schweiger, Meike and Prtvar, Danilo and Shi, Yuan and
                      Banati, Richard B and Liu, Guo-Jun and Middleton, Ryan J and
                      Mitteregger-Kretzschmar, Gerda and Perneczky, Robert and
                      Koeglsperger, Thomas and Neher, Jonas J and Tahirovic,
                      Sabina and Brendel, Matthias and Herms, Jochen and Paeger,
                      Lars},
      title        = {{E}arly {L}ocus {C}oeruleus noradrenergic axon loss drives
                      olfactory dysfunction in {A}lzheimer's disease.},
      journal      = {Nature Communications},
      volume       = {16},
      number       = {1},
      issn         = {2041-1723},
      address      = {[London]},
      publisher    = {Springer Nature},
      reportid     = {DZNE-2025-00939},
      pages        = {7338},
      year         = {2025},
      abstract     = {Alzheimer's disease (AD) often begins with non-cognitive
                      symptoms such as olfactory deficits, which can predict later
                      cognitive decline, though the mechanisms remain unclear.
                      Pathologically, the brainstem locus coeruleus (LC), the main
                      source of the neurotransmitter noradrenalin (NA) modulating
                      olfactory information processing is affected early. Here we
                      show early and distinct loss of noradrenergic input to the
                      olfactory bulb (OB) coinciding with impaired olfaction in an
                      AD mouse model, before appearance of amyloid plaques.
                      Mechanistically, OB microglia recognize and phagocytose LC
                      axons. Reducing phagocytosis genetically preserves LC axons
                      and olfaction. Prodromal AD patients display elevated
                      TSPO-PET signals in the OB, similarly to AppNL-G-F mice. We
                      further confirm early LC axon degeneration in post-mortem
                      OBs in patients with early AD. Our findings reveal a
                      mechanism linking early LC damage to hyposmia in AD,
                      suggesting olfactory testing and neurocircuit imaging for
                      early diagnosis and enable timely therapeutic intervention
                      for Alzheimer's disease.},
      keywords     = {Alzheimer Disease: pathology / Alzheimer Disease:
                      physiopathology / Alzheimer Disease: metabolism / Alzheimer
                      Disease: diagnostic imaging / Alzheimer Disease:
                      complications / Locus Coeruleus: pathology / Locus
                      Coeruleus: metabolism / Animals / Humans / Axons: pathology
                      / Axons: metabolism / Olfactory Bulb: pathology / Olfactory
                      Bulb: metabolism / Olfactory Bulb: physiopathology / Mice /
                      Male / Disease Models, Animal / Female / Mice, Transgenic /
                      Microglia: metabolism / Microglia: pathology /
                      Norepinephrine: metabolism / Aged / Phagocytosis /
                      Adrenergic Neurons: pathology / Adrenergic Neurons:
                      metabolism / Olfaction Disorders: pathology / Amyloid
                      beta-Protein Precursor: genetics / Amyloid beta-Protein
                      Precursor: metabolism / Smell: physiology / Aged, 80 and
                      over / Mice, Inbred C57BL / Plaque, Amyloid: pathology /
                      Norepinephrine (NLM Chemicals) / Amyloid beta-Protein
                      Precursor (NLM Chemicals)},
      cin          = {AG Herms / AG Garthe / AG Tahirovic / AG Neher (München) /
                      AG Dichgans / Clinical Research (Munich) / AG Haass},
      ddc          = {500},
      cid          = {I:(DE-2719)1110001 / I:(DE-2719)1740001 /
                      I:(DE-2719)1140003 / I:(DE-2719)1110011 / I:(DE-2719)5000022
                      / I:(DE-2719)1111015 / I:(DE-2719)1110007},
      pnm          = {352 - Disease Mechanisms (POF4-352) / 353 - Clinical and
                      Health Care Research (POF4-353)},
      pid          = {G:(DE-HGF)POF4-352 / G:(DE-HGF)POF4-353},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:40781079},
      pmc          = {pmc:PMC12334674},
      doi          = {10.1038/s41467-025-62500-8},
      url          = {https://pub.dzne.de/record/280284},
}