Olfactory dysfunction correlates with amyloid-βburden 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.Weaddressed 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-βprecursor 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 Aβdeposition. 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 Aβdeposition and thus may serve to monitor the efficacy of therapies aimed at reducing Aβ. Copyright © 2010 the authors.