Gene expression profiles in the olfactory bulb from a rat model of Alzheimer's disease.

Abnormalities and impaired functions of the olfactory system have been reported in Alzheimer's disease (AD), and these changes may appear much earlier than other clinical symptoms of AD. However, little is known about these abnormalities at the level of gene expression. In this study, we investigated alterations of expression of 22,012 genes in the olfactory bulbs of a rat model of AD by using a microarray approach. The rat model was produced by intracerebroventricular injection of amyloid-beta(25-35), which demonstrated pathological changes in olfactory bulbs and memory impairment in the Morris water maze test. We found that expression of 811 genes among the 22,012 genes was altered by more than 1.5-fold in the amyloid-beta-injected rats as compared with control injected rats. We analyzed the distribution of the 811 altered genes according to the Affymetrix criteria and found that the majority of these genes were related to cellular processes, binding, and enzyme activities. The alterations of three of these genes, i.e., calcineurin, olfactory receptor, and protein kinase C, were also confirmed by RT-PCR and Western blots. These studies provide new insight into the abnormalities of the olfactory system in AD and might help to further the understanding of the molecular mechanisms of AD.