Olfactory dysfunction in the 3xTg-AD model of Alzheimer’s disease

• Published in: IBRO neuroscience reports 2021-06, Vol.10, p.51-61
• Main Authors: Mitrano, Darlene A., Houle, Sam E., Pearce, Patrick, Quintanilla, Ricardo M., Lockhart, Blakely K., Genovese, Benjamin C., Schendzielos, Rachel A., Croushore, Emma E., Dymond, Ethan M., Bogenpohl, James W., Grau, Harold J., Webb, Lisa Smith
• Format: Article
• Language: English
• Subjects: 3xTg-AD; Alzheimer’s; Buried food test; Congo red; Olfaction; Research Paper
• ISSN: 2667-2421; 2667-2421
• DOI: 10.1016/j.ibneur.2020.12.004

Alzheimer’s disease (AD) is an incurable neurodegenerative disease in which the risk of development increases with age. People with AD are plagued with deficits in their cognition, memory, and basic social skills. Many of these deficits are believed to be caused by the formation of amyloid-β plaques and neurofibrillary tangles in regions of the brain associated with memory, such as the hippocampus. However, one of the early, preclinical symptoms of AD is the loss of olfactory detection and discrimination. To determine if a mouse model of AD expresses the same olfactory dysfunction seen in human AD, 3xTg-AD mice were given a buried food test and, unlike previous studies, compared to their background and parental strains. Results showed that over 52 weeks, the 3xTg-AD mice took significantly longer to find the buried food than the control strains. The olfactory bulbs of the 3xTg-AD mice were removed, sliced, and stained using Congo red for histological analysis. Amyloid deposits were observed predominantly in the granule layer of the olfactory bulb beginning at 13 weeks of age in 3xTg-AD mice, but not in the control strains of mice. Further examination of the buried food test data revealed that 3xTg-AD females had a significantly longer latency to detect the buried food than males beginning at 26 weeks of age. Overall, this study provides further validation of the 3xTg-AD mouse model of AD and supports the idea that simple olfactory testing could be part of the diagnostic process for human AD. •3xTg-AD mice perform worse than their background and parental strains on a buried food test.•Using Congo red, amyloid deposits were found in the granule and external plexiform layers of the OBs of the 3xTg-AD mice.•Female 3xTg-AD mice took significantly longer than male 3xTg-AD mice in the buried food task.•This study supports the idea of examining olfactory deficits as part of the screening and diagnosis for AD.