| 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 Publication | JOURNAL OF ALZHEIMERS DISEASE
 |
| ISSN | 1387-2877 |
| Volume | 37Issue:4Pages:699-712 |
| Abstract | 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.; 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. |
| Subtype | Article |
| Keyword | a 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 |
| DOI | 10.3233/JAD-122443 |
| WOS Headings | Science & Technology ; Life Sciences & Biomedicine |
| Funding Organization | 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] ; Natural National Science Foundation of China [31000494, 30788002, 20921004, 21105116] |
| Indexed By | SCI |
| Language | 英语 |
| WOS Research Area | Neurosciences & Neurology |
| WOS Subject | Neurosciences |
| WOS ID | WOS:000325649500006 |
| WOS Keyword | MOUSE MODEL ; A-BETA ; ORBITOFRONTAL CORTEX ; MARKER PROTEIN ; RAT-BRAIN ; MEMORY ; SYSTEM ; IMPAIRMENT ; DISORDERS ; OLIGOMERS |
| Funding Organization | 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] ; Natural National Science Foundation of China [31000494, 30788002, 20921004, 21105116] |
| Citation statistics | |
| Document Type | 期刊论文 |
| Identifier | http://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 Author | 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. |
| Affiliation | 1.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. |
| Files in This Item: | ||||||
| File Name/Size | DocType | Version | Access | License | ||
| Amyloid-beta Deposit（791KB） | 开放获取 | CC BY-NC-SA | View Application Full Text | |||
Items in the repository are protected by copyright, with all rights reserved, unless otherwise indicated.
Edit Comment