Date of Award
Honors Thesis (Open Access)
Colby College. Psychology Dept.
The hApoE4 allele is one of the strongest genetic risk factors for Alzheimer’s disease (AD). It underlies amyloid-bdeposits and neurofibrillary tangles, the two hallmarks associated with AD pathology, and is subsequently associated with AD symptomology. Despite its importance, no rat animal studies to date use hApoE4 knock-ins. In addition to this deficit in the field of AD literature, the vast majority of AD studies focus on memory, even though executive function deficits may precede memory impairments in AD, and may be a predictor of AD development. Thus, the present study addressed these gaps in AD research by investigating the behavioral and physiological changes induced in rat models by an hApoE4 knock-in. hApoE4 rats experienced heightened anxiety compared to their wildtype counterparts, with male rats showing greater anxiety than females. hApoE4 rats had reduced motor capabilities, with males being disproportionately affected compared to females. Limited spatial learning and memory deficits were found at this time, but hApoE4 rats exemplified regressive behaviors in the probe trial of the spatial learning and memory task, indicating impairment in cognitive flexibility at this age. hApoE4 rats had impaired attentional set shifting abilities, with robust effects visualized in male hApoE4 rats. There was no difference in corticosterone levels between rats. Female hApoE4 rats were more sensitive to the hApoE4 knock-in compared to males, with more than half of the female hApoE4 rats failing to finish all measures due to the lethality of the knock-in. These results indicate that the hApoE4 knock-in effectively induced AD-like pathology in rat animal models, potentially to a lethal point in females. Executive function deficits appeared to precede spatial learning and memory deficits, indicating that future clinical interventions for AD should focus on identification of executive dysfunction.
Alzheimer's disease, Executive function, Cognitive flexibility, Rat, Set-shifting, ApoE4
Recommended CitationMcManus, Kaitlin, "Executive Function Deficit as a Precursor to Memory Impairments in hApoE4 Transgenic Rats" (2020). Honors Theses. Paper 1285.