Olfactory Dysfunction Correlates with Amyloid-β Burden in an Alzheimer's Disease Mouse Model

Abstract

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-β (Aβ) deposition throughout the olfactory system in mice that overexpress a mutated form of the human amyloid-β 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 Aβ 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 Aβ deposition. Therefore, nonfibrillar, versus fibrillar, Aβ-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 Aβ deposition and thus may serve to monitor the efficacy of therapies aimed at reducing Aβ.