Olfactory sensitivity study as a possible biomarker of experimental Alzheimer's Disease in animals of the Wistar audiogenic rat (WAR) strain

Abstract

Olfactory sensitivity has been shown as an important factor in the research of neurodegenerative diseases such as Alzheimer's disease, which is characterized mainly by substantial memory loss. Recent studies have shown that olfactory loss can be used as biomarker, with predictive value, during the development of such disease. In this context, this project research seeks to associate olfactory sensitivity and Alzheimer's disease. Therefore it will be interesting to verify the olfactory sensitivity in animals of the Wistar Audiogenic Rat (WAR) strain, and their Wistar strain counterparts at three different ages: 2 months (young), 6 months (adult) and 12 months (old). Furthermore, assess whether there is connection between olfactory loss and memory loss in WARs, and finally detect possible changes in the expression of molecular markers of Alzheimer's disease in animals of the WAR strain. To achieve these objectives three groups of each strain (n = 15 animals/each age group) will be tested for olfactory sensitivity, by applying the block and the buried food tests. For memory evaluation, it will be used the Morris Water Maze Test. Subsequently the brains of WARs will be analyzed biochemically in order to verify the levels of beta-amyloid and tau proteins (phospho-tau) in Cerebellum, Hippocampus and Frontal Cortex.In order to demonstrate the viability of these experimental protocols, preliminary tests were conducted with a group of 11 WARs of which 5 were adults and 6 were elderly. The results obtained from the buried food test revealed an increased olfactory deficit in adult animals when compared with the oldest ones. These data are in agreement with those obtained previously in our Laboratory that showed larger amount of beta-amyloid aggregates in adult animals. Based on these initial data, the present study seems to demonstrate that the olfactory loss may be considered a biochemical marker of Alzheimer's disease, and strongly suggest that this sensory deficit can be used as an early predictive feature of this disease. (AU)