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@MISC{Strbing:283033,
author = {Strübing, Felix and Paeger, Lars and Klaus, Carolin and
Herms, Jochen},
title = {{L}ocus {C}oeruleus noradrenergic axon loss drives
olfactory dysfunction in {A}lzheimer's disease},
publisher = {Gene Expression Omnibus},
reportid = {DZNE-2025-01445},
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 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.},
cin = {AG Herms},
cid = {I:(DE-2719)1110001},
pnm = {352 - Disease Mechanisms (POF4-352)},
pid = {G:(DE-HGF)POF4-352},
typ = {PUB:(DE-HGF)32},
url = {https://pub.dzne.de/record/283033},
}