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Amyloid-beta Deposition and Olfactory Dysfunction in an Alzheimer's Disease Model
Wu, Nan1,2; Rao, Xiaoping1,3; Gao, Yunling1,3; Wang, Jie1; Xu, Fuqiang1; Wu, N (reprint author), Chinese Acad Sci, Wuhan Inst Phys & Math, State Key Lab Magnet Resonance Atom & Mol Phys, 7 Donghu South Rd, Wuhan 430072, Peoples R China.
2013
Source PublicationJOURNAL OF ALZHEIMERS DISEASE
ISSN1387-2877
Volume37Issue:4Pages:699-712
AbstractOlfactory 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 A beta PP/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-beta (A beta): 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 A beta 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 A beta aggregates from a very early age in the olfactory epithelium, indicating early olfactory sensory neuron degeneration in the A beta PP/PS1 mouse as in AD patients. The current data suggest that the early deposition of soluble A beta 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.; 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 A beta PP/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-beta (A beta): 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 A beta 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 A beta aggregates from a very early age in the olfactory epithelium, indicating early olfactory sensory neuron degeneration in the A beta PP/PS1 mouse as in AD patients. The current data suggest that the early deposition of soluble A beta 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.
SubtypeArticle
Keyworda Beta Deposition Pattern a Beta Pp/ps1 Transgenic Mice Alzheimer's Disease Olfactory System
Department[Wu, Nan ; Rao, Xiaoping ; Gao, Yunling ; Wang, Jie ; Xu, Fuqiang] Chinese Acad Sci, Wuhan Inst Phys & Math, State Key Lab Magnet Resonance Atom & Mol Phys, Wuhan 430072, Peoples R China ; [Wu, Nan] Chinese Acad Sci, Inst Hydrobiol, Ctr Water Environm & Human Hlth, State Key Lab Freshwater Ecol & Biotechnol, Wuhan 430072, Peoples R China ; [Rao, Xiaoping ; Gao, Yunling] Univ Chinese Acad Sci, Beijing, Peoples R China
DOI10.3233/JAD-122443
WOS HeadingsScience & Technology ; Life Sciences & Biomedicine
Funding OrganizationNatural National Science Foundation of China [31000494, 30788002, 20921004, 21105116] ; Natural National Science Foundation of China [31000494, 30788002, 20921004, 21105116] ; Natural National Science Foundation of China [31000494, 30788002, 20921004, 21105116] ; Natural National Science Foundation of China [31000494, 30788002, 20921004, 21105116]
Indexed BySCI
Language英语
WOS Research AreaNeurosciences & Neurology
WOS SubjectNeurosciences
WOS IDWOS:000325649500006
WOS KeywordMOUSE MODEL ; A-BETA ; ORBITOFRONTAL CORTEX ; MARKER PROTEIN ; RAT-BRAIN ; MEMORY ; SYSTEM ; IMPAIRMENT ; DISORDERS ; OLIGOMERS
Funding OrganizationNatural National Science Foundation of China [31000494, 30788002, 20921004, 21105116] ; Natural National Science Foundation of China [31000494, 30788002, 20921004, 21105116] ; Natural National Science Foundation of China [31000494, 30788002, 20921004, 21105116] ; Natural National Science Foundation of China [31000494, 30788002, 20921004, 21105116]
Citation statistics
Cited Times:33[WOS]   [WOS Record]     [Related Records in WOS]
Document Type期刊论文
Identifierhttp://ir.ihb.ac.cn/handle/342005/19616
Collection水生生物分子与细胞生物学研究中心_期刊论文
Corresponding AuthorWu, N (reprint author), Chinese Acad Sci, Wuhan Inst Phys & Math, State Key Lab Magnet Resonance Atom & Mol Phys, 7 Donghu South Rd, Wuhan 430072, Peoples R China.
Affiliation1.Chinese Acad Sci, Wuhan Inst Phys & Math, State Key Lab Magnet Resonance Atom & Mol Phys, Wuhan 430072, Peoples R China
2.Chinese Acad Sci, Inst Hydrobiol, Ctr Water Environm & Human Hlth, State Key Lab Freshwater Ecol & Biotechnol, Wuhan 430072, Peoples R China
3.Univ Chinese Acad Sci, Beijing, Peoples R China
Recommended Citation
GB/T 7714
Wu, Nan,Rao, Xiaoping,Gao, Yunling,et al. Amyloid-beta Deposition and Olfactory Dysfunction in an Alzheimer's Disease Model[J]. JOURNAL OF ALZHEIMERS DISEASE,2013,37(4):699-712.
APA Wu, Nan,Rao, Xiaoping,Gao, Yunling,Wang, Jie,Xu, Fuqiang,&Wu, N .(2013).Amyloid-beta Deposition and Olfactory Dysfunction in an Alzheimer's Disease Model.JOURNAL OF ALZHEIMERS DISEASE,37(4),699-712.
MLA Wu, Nan,et al."Amyloid-beta Deposition and Olfactory Dysfunction in an Alzheimer's Disease Model".JOURNAL OF ALZHEIMERS DISEASE 37.4(2013):699-712.
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