期刊
JOURNAL OF NEUROSCIENCE
卷 30, 期 2, 页码 505-514出版社
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.4622-09.2010
关键词
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资金
- National Institutes of Health [DC003906, AG017617]
- Alzheimer's Association [IIRG0759699]
Alzheimer's disease often results in impaired olfactory perceptual acuity-a potential biomarker of the disorder. However, the usefulness of olfactory screens to serve as informative indicators of Alzheimer's is precluded by a lack of knowledge regarding why the disease impacts olfaction. We addressed this question by assaying olfactory perception and amyloid-beta(A beta) deposition throughout the olfactory system in mice that overexpress a mutated form of the human amyloid-beta precursor protein. Such mice displayed progressive olfactory deficits that mimic those observed clinically-some evident at 3 months of age. Also, at 3 months of age, we observed nonfibrillar A beta deposition within the olfactory bulb-earlier than deposition within any other brain region. There was also a correlation between olfactory deficits and the spatial-temporal pattern of A beta deposition. Therefore, nonfibrillar, versus fibrillar, A beta-related mechanisms likely contribute to early olfactory perceptual loss in Alzheimer's disease. Furthermore, these results present the odor cross-habituation test as a powerful behavioral assay, which reflects A beta deposition and thus may serve to monitor the efficacy of therapies aimed at reducing A beta.
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