P4‐044: Differences in Olfactory Detection and Response Bias in the 3XTG‐AD and 5XFAD Mouse Models of Alzheimer's Disease

Olfactory dysfunction has been identified as a symptom of Alzheimer's disease (AD) that appears prior to more severe cognitive impairments, and has been proposed as a possible method of early diagnosis. The 3xTg-AD mouse model of AD develops amyloid and tau pathology due to mutations to amyloid precursor protein, presenilin 1, and tau, while the 5XFAD mouse model develops amyloid but not tau pathology due to three mutations to amyloid precursor protein and two mutations to presenilin 1. We investigated these two commonly used mouse models for changes in olfactory function. Female and male 3xTg-AD mice and 5XFAD mice, and their wildtype controls, were tested at six months of age using an automated olfactometer. Mice were presented with decreasing concentrations of ethyl acetate on a go no-go odour detection task. Female 3xTg-AD mice had decreased detection of the odour compared to their wildtype controls and showed a more liberal response bias. There was no difference between male 3xTg-AD mice and their wildtype controls. 5XFAD mice did not differ from their wildtype controls on odour detection, but did show a less liberal response bias. There was also a sex difference in the 5xFAD model and their wildtype controls, with the female mice displaying greater detection than male mice, and a less liberal response bias than the males. Olfactory detection appears to be impaired in female 3xTg-AD mice, but not in male 3xTg-AD mice. No such impairment is seen in the either sex of the 5XFAD mice, though female 5XFAD mice did perform better than male 5XFAD mice. The changes in response bias seen in the female 3xTg-AD and 5XFAD mice of both sexes suggests there are alterations in cognitive function of both model that affected performance on this task.