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Hippocampus-related cognitive impairments in young apoE4 targeted replacement mice
Shiran Salomon-Zimri1, Anat Boehm-Cagan, Ori Liraz
1Department of Neurobiology, George S. Wise Faculty of Life Sciences, Sagol School of Neuroscience, Tel Aviv University, Tel Aviv, Israel.
Abstract:
We presently investigated the effects of apolipoprotein E4 (apoE4), the most prevalent genetic risk factor for Alzheimer's disease, on the cognitive performance of young targeted replacement apoE4 mice. We revealed that these mice were impaired in the object recognition and Morris water maze tests, both of which are associated with hippocampal learning and memory, relative to that of the apoE3 mice. These results are consistent with previous histological and biochemical findings that hippocampal neurons are specifically affected by apoE4. The suggestion that the behavioral impairments of the apoE4 mice are related to the hippocampal neuropathology of these mice is further supported by the fear conditioning test. This test revealed that the performance of the apoE4 mice in the contextual component, which is hippocampus related, was impaired, whereas their cued test response, which is amygdala driven, was not. The stress levels of the apoE4 and apoE3 mice, as unraveled by the light/dark anxiety test, were similar, suggesting that the observed cognitive impairments of the apoE4 mice are not related to differences in the basal anxiety levels of these mice. In conclusion, the present study shows that young apoE4 targeted replacement mice are impaired in numerous hippocampus-related learning and memory tasks.
Insights
Young mice carrying the apolipoprotein E4 (apoE4) gene show significant impairments in hippocampus-dependent learning and memory tasks. These findings suggest apoE4 impacts cognitive function early in life, potentially contributing to Alzheimer's disease risk.
Area of Science:
- Neuroscience
- Genetics
- Cognitive Science
Background:
- Apolipoprotein E4 (apoE4) is the primary genetic risk factor for Alzheimer's disease (AD).
- Previous studies indicate apoE4 affects hippocampal structure and function.
- Understanding apoE4's early cognitive effects is crucial for AD research.
Purpose of the Study:
- To investigate the impact of apoE4 on cognitive performance in young mice.
- To determine if apoE4-associated cognitive deficits are linked to hippocampal function.
Main Methods:
- Utilized targeted replacement apoE4 (TR apoE4) and apoE3 (TR apoE3) mice.
- Assessed cognitive performance using object recognition, Morris water maze, and fear conditioning tests.
- Measured anxiety levels via the light/dark anxiety test.
Main Results:
- TR apoE4 mice exhibited significant impairments in object recognition and Morris water maze tasks compared to TR apoE3 mice.
- Fear conditioning results showed deficits in hippocampus-dependent contextual memory but not amygdala-dependent cued memory in TR apoE4 mice.
- No significant differences in basal anxiety levels were observed between TR apoE4 and TR apoE3 mice.
Conclusions:
- Young TR apoE4 mice display deficits in multiple hippocampus-related learning and memory functions.
- These cognitive impairments are likely due to apoE4's specific effects on hippocampal neuropathology.
- The study highlights early-life cognitive consequences of the apoE4 genotype relevant to Alzheimer's disease pathogenesis.
