Olfactory dysfunction correlates with amyloid-beta burden in an Alzheimer's disease mouse model.
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 (Abeta) 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 Abeta 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 Abeta deposition. Therefore, nonfibrillar, versus fibrillar, Abeta-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 Abeta deposition and thus may serve to monitor the efficacy of therapies aimed at reducing Abeta.
Wesson
Daniel W
DW
Emotional Brain Institute and Center for Dementia Research, Nathan S. Kline Institute for Psychiatric Research, Orangeburg, New York 10962, USA. dwesson@nki.rfmh.org
Levy
Efrat
E
Nixon
Ralph A
RA
Wilson
Donald A
DA
D000367:Age Factors; D000544:Alzheimer Disease / Q000150:complications* / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000704:Analysis of Variance; D000818:Animals; D004192:Discrimination, Psychological / Q000502:physiology; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000235:genetics; D006185:Habituation, Psychophysiologic / Q000235:genetics; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D009812:Odorants; D009833:Olfactory Pathways / Q000378:metabolism; D055696:Olfactory Perception / Q000502:physiology*; D010468:Perceptual Disorders / Q000209:etiology*
D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor