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Updated: Jun 17, 2026
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Olfactory Assays for Mouse Models of Neurodegenerative Disease
Published on: August 25, 2014
Olfactory dysfunction correlates with amyloid-beta burden in an Alzheimer's disease mouse model
Daniel W Wesson1, Efrat Levy, Ralph A Nixon
1Emotional Brain Institute and Center for Dementia Research, Nathan S. Kline Institute for Psychiatric Research, Orangeburg, New York 10962, USA. dwesson@nki.rfmh.org
Summary
Alzheimer's disease impairs smell early due to amyloid-beta (Abeta) buildup in the olfactory bulb. This finding highlights smell tests as potential Alzheimer's biomarkers and therapy monitors.
Area of Science:
- Neuroscience
- Biomarkers
- Neurodegenerative Diseases
Background:
- Alzheimer's disease (AD) is linked to olfactory dysfunction.
- The precise mechanisms causing smell impairment in AD remain unclear.
- Olfactory deficits may serve as an early biomarker for AD.
Purpose of the Study:
- To investigate the relationship between amyloid-beta (Abeta) deposition and olfactory deficits in a mouse model of Alzheimer's disease.
- To determine if early Abeta deposition in the olfactory system precedes cognitive decline.
- To evaluate the potential of olfactory tests as biomarkers for AD progression and therapeutic response.
Main Methods:
- Assayed olfactory perception and Abeta deposition in transgenic mice overexpressing mutated amyloid precursor protein.
- Examined Abeta deposition patterns throughout the olfactory system.
- Utilized an odor cross-habituation test to assess olfactory function.
Main Results:
- Mice exhibited progressive olfactory deficits starting at 3 months of age, mirroring clinical observations in AD.
- Non-fibrillar Abeta deposition was detected in the olfactory bulb at 3 months, preceding deposition in other brain regions.
- A correlation was found between the severity of olfactory deficits and the spatial-temporal pattern of Abeta deposition.
Conclusions:
- Non-fibrillar Abeta, rather than fibrillar, likely drives early olfactory perceptual loss in Alzheimer's disease.
- The odor cross-habituation test is a sensitive behavioral assay reflecting Abeta deposition.
- Olfactory screens show promise for monitoring AD progression and evaluating anti-Abeta therapies.
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