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Human Apolipoprotein E Genotype Differentially Affects Olfactory Behavior and Sensory Physiology in Mice
Brett S East1, Gloria Fleming2, Kathy Peng3
1Emotional Brain Institute, Nathan S. Kline Institute, Orangeburg, NY 10962, USA; Department of Child & Adolescent Psychiatry, New York University School of Medicine, New York, NY 10016, USA.
Neuroscience
|April 22, 2018
Summary
Apolipoprotein E (ApoE) genotype influences olfactory system function. ApoE4 impairs odor habituation and increases excitability, while ApoE2 shows protective effects, offering early biomarkers for neurodegeneration risk.
Area of Science:
- Neuroscience
- Genetics
- Olfactory System Research
Background:
- Apolipoprotein E (ApoE) is crucial for lipid transport in the brain and periphery.
- The ApoE ε4 allele (ApoE4) is a major genetic risk factor for Alzheimer's disease (AD), while ApoE2 is protective.
- The olfactory system may reveal early effects of ApoE genotype on neural circuits.
Purpose of the Study:
- To investigate the impact of different human Apolipoprotein E (ApoE) genotypes (ApoE2, ApoE3, ApoE4) on olfactory behavior and physiology in mice.
- To determine if ApoE genotype affects olfactory system function prior to Alzheimer's disease pathology.
Main Methods:
- Comparison of olfactory behavior (odor investigation, habituation) in 6- and 12-month-old mice with targeted replacement for human ApoE2, ApoE3, or ApoE4.
- Assessment of olfactory bulb and piriform cortex local field potential activity to measure system excitability and odor responsiveness.
Main Results:
- Odor habituation was impaired in ApoE4 mice compared to ApoE2 mice; ApoE3 mice showed intermediate function.
- Odor habituation significantly deteriorated with age (6 to 12 months) across all genotypes.
- Olfactory system excitability followed an ApoE4 > ApoE3 > ApoE2 ranking, with ApoE4 mice exhibiting hyper-excitability and ApoE2 mice showing hypo-excitability.
Conclusions:
- ApoE genotype significantly impacts olfactory system function, affecting odor habituation and neural excitability.
- The observed hyper-excitability in ApoE4 mice may contribute to impaired habituation, while hypo-excitability in ApoE2 mice might confer protection.
- These findings highlight the role of ApoE in early-stage olfactory system changes, preceding AD pathology.
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