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000303450 1001_ $$aMeyer, Carolin$$b0
000303450 245__ $$aEarly Locus Coeruleus noradrenergic axon loss drives olfactory dysfunction in Alzheimer's disease.
000303450 260__ $$a[London]$$bSpringer Nature$$c2025
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000303450 520__ $$aAlzheimer's disease (AD) often begins with non-cognitive symptoms such as olfactory deficits, which can predict later cognitive decline, though the mechanisms remain unclear. Pathologically, the brainstem locus coeruleus (LC), the main source of the neurotransmitter noradrenalin (NA) modulating olfactory information processing is affected early. Here we show early and distinct loss of noradrenergic input to the olfactory bulb (OB) coinciding with impaired olfaction in an AD mouse model, before appearance of amyloid plaques. Mechanistically, OB microglia recognize and phagocytose LC axons. Reducing phagocytosis genetically preserves LC axons and olfaction. Prodromal AD patients display elevated TSPO-PET signals in the OB, similarly to AppNL-G-F mice. We further confirm early LC axon degeneration in post-mortem OBs in patients with early AD. Our findings reveal a mechanism linking early LC damage to hyposmia in AD, suggesting olfactory testing and neurocircuit imaging for early diagnosis and enable timely therapeutic intervention for Alzheimer's disease.
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000303450 650_7 $$0X4W3ENH1CV$$2NLM Chemicals$$aNorepinephrine
000303450 650_7 $$2NLM Chemicals$$aAmyloid beta-Protein Precursor
000303450 650_2 $$2MeSH$$aAlzheimer Disease: pathology
000303450 650_2 $$2MeSH$$aAlzheimer Disease: physiopathology
000303450 650_2 $$2MeSH$$aAlzheimer Disease: metabolism
000303450 650_2 $$2MeSH$$aAlzheimer Disease: diagnostic imaging
000303450 650_2 $$2MeSH$$aAlzheimer Disease: complications
000303450 650_2 $$2MeSH$$aLocus Coeruleus: pathology
000303450 650_2 $$2MeSH$$aLocus Coeruleus: metabolism
000303450 650_2 $$2MeSH$$aAnimals
000303450 650_2 $$2MeSH$$aHumans
000303450 650_2 $$2MeSH$$aAxons: pathology
000303450 650_2 $$2MeSH$$aAxons: metabolism
000303450 650_2 $$2MeSH$$aOlfactory Bulb: pathology
000303450 650_2 $$2MeSH$$aOlfactory Bulb: metabolism
000303450 650_2 $$2MeSH$$aOlfactory Bulb: physiopathology
000303450 650_2 $$2MeSH$$aMice
000303450 650_2 $$2MeSH$$aMale
000303450 650_2 $$2MeSH$$aDisease Models, Animal
000303450 650_2 $$2MeSH$$aFemale
000303450 650_2 $$2MeSH$$aMice, Transgenic
000303450 650_2 $$2MeSH$$aMicroglia: metabolism
000303450 650_2 $$2MeSH$$aMicroglia: pathology
000303450 650_2 $$2MeSH$$aNorepinephrine: metabolism
000303450 650_2 $$2MeSH$$aAged
000303450 650_2 $$2MeSH$$aPhagocytosis
000303450 650_2 $$2MeSH$$aAdrenergic Neurons: pathology
000303450 650_2 $$2MeSH$$aAdrenergic Neurons: metabolism
000303450 650_2 $$2MeSH$$aOlfaction Disorders: pathology
000303450 650_2 $$2MeSH$$aAmyloid beta-Protein Precursor: genetics
000303450 650_2 $$2MeSH$$aAmyloid beta-Protein Precursor: metabolism
000303450 650_2 $$2MeSH$$aSmell: physiology
000303450 650_2 $$2MeSH$$aAged, 80 and over
000303450 650_2 $$2MeSH$$aMice, Inbred C57BL
000303450 650_2 $$2MeSH$$aPlaque, Amyloid: pathology
000303450 7001_ $$00009-0009-2257-5394$$aNiedermeier, Theresa$$b1
000303450 7001_ $$aFeyen, Paul L C$$b2
000303450 7001_ $$00000-0002-9436-6294$$aStrübing, Felix L$$b3
000303450 7001_ $$00000-0003-4547-6240$$aRauchmann, Boris-Stephan$$b4
000303450 7001_ $$aKarali, Katerina$$b5
000303450 7001_ $$aGentz, Johanna$$b6
000303450 7001_ $$00009-0005-0828-3425$$aTillmann, Yannik E$$b7
000303450 7001_ $$00009-0003-9134-6575$$aLandgraf, Nicolas F$$b8
000303450 7001_ $$aRumpf, Svenja-Lotta$$b9
000303450 7001_ $$aOchs, Katharina$$b10
000303450 7001_ $$aWind-Mark, Karin$$b11
000303450 7001_ $$00009-0008-5161-9571$$aBiechele, Gloria$$b12
000303450 7001_ $$aWagner, Jessica$$b13
000303450 7001_ $$00000-0001-6714-5827$$aGuersel, Selim$$b14
000303450 7001_ $$00000-0003-4299-6240$$aKurz, Carolin I$$b15
000303450 7001_ $$aSchweiger, Meike$$b16
000303450 7001_ $$aPrtvar, Danilo$$b17
000303450 7001_ $$00000-0001-6135-1830$$aShi, Yuan$$b18
000303450 7001_ $$00000-0003-3558-597X$$aBanati, Richard B$$b19
000303450 7001_ $$00000-0002-4278-8372$$aLiu, Guo-Jun$$b20
000303450 7001_ $$aMiddleton, Ryan J$$b21
000303450 7001_ $$aMitteregger-Kretzschmar, Gerda$$b22
000303450 7001_ $$00000-0003-1981-7435$$aPerneczky, Robert$$b23
000303450 7001_ $$aKoeglsperger, Thomas$$b24
000303450 7001_ $$00000-0003-1346-8924$$aNeher, Jonas J$$b25
000303450 7001_ $$00000-0003-4403-9559$$aTahirovic, Sabina$$b26
000303450 7001_ $$00000-0002-9247-2843$$aBrendel, Matthias$$b27
000303450 7001_ $$00000-0002-6201-1042$$aHerms, Jochen$$b28
000303450 7001_ $$00000-0001-8716-3483$$aPaeger, Lars$$b29
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