000283033 001__ 283033
000283033 005__ 20251222135312.0
000283033 037__ $$aDZNE-2025-01445
000283033 1001_ $$0P:(DE-2719)2813904$$aStrübing, Felix$$b0$$udzne
000283033 245__ $$aLocus Coeruleus noradrenergic axon loss drives olfactory dysfunction in Alzheimer's disease
000283033 260__ $$bGene Expression Omnibus$$c2025
000283033 3367_ $$2BibTeX$$aMISC
000283033 3367_ $$0PUB:(DE-HGF)32$$2PUB:(DE-HGF)$$aDataset$$bdataset$$mdataset$$s1766407975_14400
000283033 3367_ $$026$$2EndNote$$aChart or Table
000283033 3367_ $$2DataCite$$aDataset
000283033 3367_ $$2ORCID$$aDATA_SET
000283033 3367_ $$2DINI$$aResearchData
000283033 520__ $$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 ealy. 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. Importantly, patients with prodromal AD 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.
000283033 536__ $$0G:(DE-HGF)POF4-352$$a352 - Disease Mechanisms (POF4-352)$$cPOF4-352$$fPOF IV$$x0
000283033 7001_ $$0P:(DE-2719)9002242$$aPaeger, Lars$$b1$$udzne
000283033 7001_ $$0P:(DE-2719)9001221$$aKlaus, Carolin$$b2$$udzne
000283033 7001_ $$0P:(DE-2719)2810441$$aHerms, Jochen$$b3$$udzne
000283033 7870_ $$0DZNE-2025-00939$$aMeyer, Carolin et.al.$$d[London] : Springer Nature, 2025$$iRelatedTo$$r$$tEarly Locus Coeruleus noradrenergic axon loss drives olfactory dysfunction in Alzheimer's disease.
000283033 8564_ $$uhttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE302245
000283033 9101_ $$0I:(DE-588)1065079516$$6P:(DE-2719)2813904$$aDeutsches Zentrum für Neurodegenerative Erkrankungen$$b0$$kDZNE
000283033 9101_ $$0I:(DE-588)1065079516$$6P:(DE-2719)9002242$$aDeutsches Zentrum für Neurodegenerative Erkrankungen$$b1$$kDZNE
000283033 9101_ $$0I:(DE-588)1065079516$$6P:(DE-2719)9001221$$aDeutsches Zentrum für Neurodegenerative Erkrankungen$$b2$$kDZNE
000283033 9101_ $$0I:(DE-588)1065079516$$6P:(DE-2719)2810441$$aDeutsches Zentrum für Neurodegenerative Erkrankungen$$b3$$kDZNE
000283033 9131_ $$0G:(DE-HGF)POF4-352$$1G:(DE-HGF)POF4-350$$2G:(DE-HGF)POF4-300$$3G:(DE-HGF)POF4$$4G:(DE-HGF)POF$$aDE-HGF$$bGesundheit$$lNeurodegenerative Diseases$$vDisease Mechanisms$$x0
000283033 9141_ $$y2025
000283033 9201_ $$0I:(DE-2719)1110001$$kAG Herms$$lTranslational Brain Research$$x0
000283033 980__ $$adataset
000283033 980__ $$aEDITORS
000283033 980__ $$aVDBINPRINT
000283033 980__ $$aI:(DE-2719)1110001
000283033 980__ $$aUNRESTRICTED