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000280284 1001_ $$0P:(DE-2719)9001221$$aMeyer, Carolin$$b0$$eFirst author$$udzne
000280284 245__ $$aEarly Locus Coeruleus noradrenergic axon loss drives olfactory dysfunction in Alzheimer's disease.
000280284 260__ $$a[London]$$bSpringer Nature$$c2025
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000280284 520__ $$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.
000280284 536__ $$0G:(DE-HGF)POF4-352$$a352 - Disease Mechanisms (POF4-352)$$cPOF4-352$$fPOF IV$$x0
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000280284 650_7 $$0X4W3ENH1CV$$2NLM Chemicals$$aNorepinephrine
000280284 650_7 $$2NLM Chemicals$$aAmyloid beta-Protein Precursor
000280284 650_2 $$2MeSH$$aAlzheimer Disease: pathology
000280284 650_2 $$2MeSH$$aAlzheimer Disease: physiopathology
000280284 650_2 $$2MeSH$$aAlzheimer Disease: metabolism
000280284 650_2 $$2MeSH$$aAlzheimer Disease: diagnostic imaging
000280284 650_2 $$2MeSH$$aAlzheimer Disease: complications
000280284 650_2 $$2MeSH$$aLocus Coeruleus: pathology
000280284 650_2 $$2MeSH$$aLocus Coeruleus: metabolism
000280284 650_2 $$2MeSH$$aAnimals
000280284 650_2 $$2MeSH$$aHumans
000280284 650_2 $$2MeSH$$aAxons: pathology
000280284 650_2 $$2MeSH$$aAxons: metabolism
000280284 650_2 $$2MeSH$$aOlfactory Bulb: pathology
000280284 650_2 $$2MeSH$$aOlfactory Bulb: metabolism
000280284 650_2 $$2MeSH$$aOlfactory Bulb: physiopathology
000280284 650_2 $$2MeSH$$aMice
000280284 650_2 $$2MeSH$$aMale
000280284 650_2 $$2MeSH$$aDisease Models, Animal
000280284 650_2 $$2MeSH$$aFemale
000280284 650_2 $$2MeSH$$aMice, Transgenic
000280284 650_2 $$2MeSH$$aMicroglia: metabolism
000280284 650_2 $$2MeSH$$aMicroglia: pathology
000280284 650_2 $$2MeSH$$aNorepinephrine: metabolism
000280284 650_2 $$2MeSH$$aAged
000280284 650_2 $$2MeSH$$aPhagocytosis
000280284 650_2 $$2MeSH$$aAdrenergic Neurons: pathology
000280284 650_2 $$2MeSH$$aAdrenergic Neurons: metabolism
000280284 650_2 $$2MeSH$$aOlfaction Disorders: pathology
000280284 650_2 $$2MeSH$$aAmyloid beta-Protein Precursor: genetics
000280284 650_2 $$2MeSH$$aAmyloid beta-Protein Precursor: metabolism
000280284 650_2 $$2MeSH$$aSmell: physiology
000280284 650_2 $$2MeSH$$aAged, 80 and over
000280284 650_2 $$2MeSH$$aMice, Inbred C57BL
000280284 650_2 $$2MeSH$$aPlaque, Amyloid: pathology
000280284 7001_ $$0P:(DE-2719)9002546$$aNiedermeier, Theresa$$b1$$udzne
000280284 7001_ $$0P:(DE-2719)9001363$$aFeyen, Paul L C$$b2$$udzne
000280284 7001_ $$0P:(DE-2719)2813904$$aStrübing, Felix L$$b3
000280284 7001_ $$0P:(DE-2719)9001808$$aRauchmann, Boris Stephan$$b4$$udzne
000280284 7001_ $$0P:(DE-2719)9002032$$aKarali, Katerina$$b5$$udzne
000280284 7001_ $$0P:(DE-2719)9002339$$aGentz, Johanna$$b6$$udzne
000280284 7001_ $$0P:(DE-2719)9002700$$aTillmann, Yannik$$b7$$udzne
000280284 7001_ $$0P:(DE-2719)9002923$$aLandgraf, Nicolas Friedrich$$b8$$udzne
000280284 7001_ $$0P:(DE-2719)9001823$$aRumpf, Svenja-Lotta$$b9$$udzne
000280284 7001_ $$0P:(DE-2719)2812681$$aOchs, Katharina$$b10$$udzne
000280284 7001_ $$0P:(DE-2719)9001653$$aWind-Mark, Karin$$b11
000280284 7001_ $$00009-0008-5161-9571$$aBiechele, Gloria$$b12
000280284 7001_ $$0P:(DE-2719)2812193$$aWagner, Jessica$$b13$$udzne
000280284 7001_ $$0P:(DE-2719)9001027$$aGuersel, Selim$$b14$$udzne
000280284 7001_ $$0P:(DE-2719)9000176$$aKurz, Carolin$$b15
000280284 7001_ $$aSchweiger, Meike$$b16
000280284 7001_ $$0P:(DE-2719)9002550$$aPrtvar, Danilo$$b17$$udzne
000280284 7001_ $$0P:(DE-2719)2811433$$aShi, Yuan$$b18$$udzne
000280284 7001_ $$00000-0003-3558-597X$$aBanati, Richard B$$b19
000280284 7001_ $$00000-0002-4278-8372$$aLiu, Guo-Jun$$b20
000280284 7001_ $$aMiddleton, Ryan J$$b21
000280284 7001_ $$aMitteregger-Kretzschmar, Gerda$$b22
000280284 7001_ $$0P:(DE-2719)2812234$$aPerneczky, Robert$$b23
000280284 7001_ $$0P:(DE-2719)2810825$$aKoeglsperger, Thomas$$b24$$udzne
000280284 7001_ $$0P:(DE-2719)2811021$$aNeher, Jonas J$$b25
000280284 7001_ $$0P:(DE-2719)2442036$$aTahirovic, Sabina$$b26
000280284 7001_ $$0P:(DE-2719)9001539$$aBrendel, Matthias$$b27
000280284 7001_ $$0P:(DE-2719)2810441$$aHerms, Jochen$$b28$$eLast author
000280284 7001_ $$0P:(DE-2719)9002242$$aPaeger, Lars$$b29$$eLast author
000280284 773__ $$0PERI:(DE-600)2553671-0$$a10.1038/s41467-025-62500-8$$gVol. 16, no. 1, p. 7338$$n1$$p7338$$tNature Communications$$v16$$x2041-1723$$y2025
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