Amyloid-β deposition and olfactory dysfunction in an Alzheimer's disease model.
Olfactory dysfunction is closely related to Alzheimer's disease (AD). Yet the mechanism behind this dysfunction remains largely unknown. To clarify the relationship between olfactory and memory deficits, we assessed behavioral and olfactory system pathology in AβPP/PS1 transgenic mice using the olfactory threshold test, the Morris water maze, Western blotting, immunohistochemistry (IHC), and thioflavine-s staining. Western blotting revealed the following spatial-temporal deposition of amyloid-β (Aβ): appeared in the olfactory epithelium at 1-2 months old (mo); expanded to the olfactory bulb at 3-4 mo; expanded to the anterior olfactory nucleus, piriform cortex, entorhinal cortex, and hippocampus at 6-7 mo; and increased with age (9-10 mo) in the more central cortices. IHC staining showed similar results, but the appearance time points for the spotty signals in these brain regions were earlier due to the higher spatial resolution compared with Western blotting. The spread of Aβ deposits from the olfactory epithelium to the olfactory bulb, the anterior olfactory nucleus, and piriform cotex (faint) at 3-4 mo correlated with the olfactory detection deficit found at the corresponding age; and the high level of depositions in the more central regions at 9-10 mo correlated with spatial memory deficit at the same age. We also found that a decline in the levels of olfactory marker protein, a marker of functioning olfactory sensory neuron, coincided with soluble Aβ aggregates from a very early age in the olfactory epithelium, indicating early olfactory sensory neuron degeneration in the AβPP/PS1 mouse as in AD patients. The current data suggest that the early deposition of soluble Aβ aggregates in the olfactory system and the early deficit in olfactory dysfunction have the potential to serve as molecular markers for the early diagnosis of AD.
State Key Laboratory of Magnetic Resonance, Atomic and Molecular Physics, Wuhan Institute of Physics and Mathematics, Chinese Academy of Sciences, Wuhan, China State Key Laboratory of Freshwater Ecology and Biotechnology, Center for Water Environment and Human Health, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, China.
Nan
N
Wu
Xiaoping
X
Rao
Yunling
Y
Gao
Jie
J
Wang
Fuqiang
F
Xu
D000367:Age Factors; D000544:Alzheimer Disease / Q000175:diagnosis / Q000235:genetics / Q000473:pathology*; D016564:Amyloid beta-Protein Precursor; D000818:Animals; D004195:Disease Models, Animal; D042241:Early Diagnosis; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D000857:Olfaction Disorders / Q000235:genetics / Q000473:pathology*; D009830:Olfactory Bulb / Q000473:pathology*; D009831:Olfactory Mucosa / Q000473:pathology*; D053764:Presenilin-1 / Q000235:genetics
D016564:Amyloid beta-Protein Precursor; C508853:PSEN1 protein, human; D053764:Presenilin-1
Alzheimer's disease; Aβ deposition pattern; AβPP/PS1 transgenic mice; olfactory system