Authors:

Denise Romero

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About Paper:

Among the list of genetic risk factors identified for Alzheimer's disease (AD), the apolipoprotein E (ApoE) gene is the most prevalent, with different alleles having different implications for A D pathology. Previous work has shown the E3 allele to be "neutral" in comparison to the E4 allele. This allele can influence neural function decades before disease onset and is associated with a host of brain changes, including increased inflammation, impaired brain energy metabolism, and compromised synaptic function, all of which impair neurotransmission and could contribute to cognitive impairments. Using homozygous ApoE transgenic rats, where the ApoE gene is excised and replaced with the human E3 or E4 gene, allows us to evaluate how genotype impacts prefrontal cortex (PFC)-mediated cognitive functions. These rats were evaluated on a battery of executive functioning tasks, including intertemporal choice, working memory, and probabilistic reversal learning, all of which can be compromised in individuals with AD. In the intertemporal choice task, rats select between a small, immediately available food reward and a large food reward delivered after a variable delay period (0-60s). In the working memory task, rats have to recall the location of a lever following a variable delay period (0-24s). In the probabilistic reversal learning task that assesses cognitive flexibility, rats have to learn to discriminate between two levers that are reinforced at different probabilities and are then switched multiple times per test session. Preliminary data on the intertemporal choice task suggests that young transgenic ApoE3 males show reduced preference for the large reward as delays increase compared to the other groups, demonstrating that they are more impulsive compared to ApoE4 males and both female genotypes. These initial findings suggest the presence of sex differences in ApoE genotype penetrance and emphasize the importance of evaluating both sexes in studies of executive functions in the context of aging and risk factors for neurodegenerative disease.

Source:

University of Florida / Denise Romero, Katherine M. Gonzalez, Sara N. Burke, Barry / 2024

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Co-authors:

Denise Romero