Home > Publications Database > Early Locus Coeruleus noradrenergic axon loss drives olfactory dysfunction in Alzheimer's disease. > print

001     280284
005     20250831001838.0
024 7 _ |a 10.1038/s41467-025-62500-8
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037 _ _ |a DZNE-2025-00939
041 _ _ |a English
082 _ _ |a 500
100 1 _ |a Meyer, Carolin
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245 _ _ |a Early Locus Coeruleus noradrenergic axon loss drives olfactory dysfunction in Alzheimer's disease.
260 _ _ |a [London]
|c 2025
|b Springer Nature
336 7 _ |a article
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336 7 _ |a ARTICLE
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520 _ _ |a 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.
536 _ _ |a 352 - Disease Mechanisms (POF4-352)
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650 _ 7 |a Norepinephrine
|0 X4W3ENH1CV
|2 NLM Chemicals
650 _ 7 |a Amyloid beta-Protein Precursor
|2 NLM Chemicals
650 _ 2 |a Alzheimer Disease: pathology
|2 MeSH
650 _ 2 |a Alzheimer Disease: physiopathology
|2 MeSH
650 _ 2 |a Alzheimer Disease: metabolism
|2 MeSH
650 _ 2 |a Alzheimer Disease: diagnostic imaging
|2 MeSH
650 _ 2 |a Alzheimer Disease: complications
|2 MeSH
650 _ 2 |a Locus Coeruleus: pathology
|2 MeSH
650 _ 2 |a Locus Coeruleus: metabolism
|2 MeSH
650 _ 2 |a Animals
|2 MeSH
650 _ 2 |a Humans
|2 MeSH
650 _ 2 |a Axons: pathology
|2 MeSH
650 _ 2 |a Axons: metabolism
|2 MeSH
650 _ 2 |a Olfactory Bulb: pathology
|2 MeSH
650 _ 2 |a Olfactory Bulb: metabolism
|2 MeSH
650 _ 2 |a Olfactory Bulb: physiopathology
|2 MeSH
650 _ 2 |a Mice
|2 MeSH
650 _ 2 |a Male
|2 MeSH
650 _ 2 |a Disease Models, Animal
|2 MeSH
650 _ 2 |a Female
|2 MeSH
650 _ 2 |a Mice, Transgenic
|2 MeSH
650 _ 2 |a Microglia: metabolism
|2 MeSH
650 _ 2 |a Microglia: pathology
|2 MeSH
650 _ 2 |a Norepinephrine: metabolism
|2 MeSH
650 _ 2 |a Aged
|2 MeSH
650 _ 2 |a Phagocytosis
|2 MeSH
650 _ 2 |a Adrenergic Neurons: pathology
|2 MeSH
650 _ 2 |a Adrenergic Neurons: metabolism
|2 MeSH
650 _ 2 |a Olfaction Disorders: pathology
|2 MeSH
650 _ 2 |a Amyloid beta-Protein Precursor: genetics
|2 MeSH
650 _ 2 |a Amyloid beta-Protein Precursor: metabolism
|2 MeSH
650 _ 2 |a Smell: physiology
|2 MeSH
650 _ 2 |a Aged, 80 and over
|2 MeSH
650 _ 2 |a Mice, Inbred C57BL
|2 MeSH
650 _ 2 |a Plaque, Amyloid: pathology
|2 MeSH
700 1 _ |a Niedermeier, Theresa
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700 1 _ |a Feyen, Paul L C
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700 1 _ |a Strübing, Felix L
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700 1 _ |a Rauchmann, Boris Stephan
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700 1 _ |a Karali, Katerina
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700 1 _ |a Gentz, Johanna
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700 1 _ |a Tillmann, Yannik
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700 1 _ |a Landgraf, Nicolas Friedrich
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700 1 _ |a Rumpf, Svenja-Lotta
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700 1 _ |a Ochs, Katharina
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700 1 _ |a Wind-Mark, Karin
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700 1 _ |a Biechele, Gloria
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700 1 _ |a Wagner, Jessica
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700 1 _ |a Guersel, Selim
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700 1 _ |a Kurz, Carolin
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700 1 _ |a Schweiger, Meike
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700 1 _ |a Prtvar, Danilo
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700 1 _ |a Shi, Yuan
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700 1 _ |a Banati, Richard B
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700 1 _ |a Liu, Guo-Jun
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700 1 _ |a Middleton, Ryan J
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700 1 _ |a Mitteregger-Kretzschmar, Gerda
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700 1 _ |a Perneczky, Robert
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700 1 _ |a Koeglsperger, Thomas
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700 1 _ |a Neher, Jonas J
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700 1 _ |a Tahirovic, Sabina
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700 1 _ |a Brendel, Matthias
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700 1 _ |a Herms, Jochen
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700 1 _ |a Paeger, Lars
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773 _ _ |a 10.1038/s41467-025-62500-8
|g Vol. 16, no. 1, p. 7338
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