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apoE isoforms and measures of anxiety in probable AD patients and Apoe-/- mice
Jennifer Robertson1, Justine Curley, Jeffrey Kaye
1Department of Behavioral Neuroscience, L470, Oregon Health and Science University, 3181 SW Sam Jackson Park Road, Portland, OR 97239, USA.
Abstract:
Increased anxiety may occur in up to 70% of AD patients during the course of their illness. Here we show that human apoE isoforms, which differ in AD risk, have differential effects on measures of anxiety in adult Apoe-/- male mice expressing human apoE3 or apoE4 in their brains and male probable AD (PRAD) patients. Compared with wild-type mice, Apoe-/- mice without human apoE or with apoE4, but not apoE3, showed increased measures of anxiety. These behavioral alterations were associated with reduced microtubule-associated protein 2-positive neuronal dendrites in the central nucleus of the amygdala. Consistent with the mouse data, male and female PRAD patients with epsilon4/epsilon4 showed higher anxiety scores than those with epsilon3/epsilon3. We conclude that human apoE isoforms have differential effects on measures of anxiety.
Insights
Apolipoprotein E (apoE) isoforms influence anxiety in Alzheimer's disease (AD) models. ApoE4, but not apoE3, increased anxiety behaviors and altered neuronal structure in mice and patients.
Area of Science:
- Neuroscience
- Genetics
- Psychiatry
Background:
- Anxiety is a common comorbidity in Alzheimer's disease (AD), affecting up to 70% of patients.
- Apolipoprotein E (apoE) isoforms, particularly apoE4, are established risk factors for AD.
- The specific impact of different human apoE isoforms on anxiety remains incompletely understood.
Purpose of the Study:
- To investigate the differential effects of human apoE3 and apoE4 isoforms on anxiety-related behaviors.
- To explore the underlying neurobiological mechanisms associated with apoE-mediated anxiety.
- To examine the correlation between apoE genotype and anxiety levels in probable AD (PRAD) patients.
Main Methods:
- Utilized adult male Apoe-/- mice expressing human apoE3 or apoE4, alongside wild-type and non-human apoE controls.
- Assessed anxiety-like behaviors in mice using established behavioral paradigms.
- Examined neuronal morphology, specifically microtubule-associated protein 2 (MAP2)-positive dendrites, in the central nucleus of the amygdala.
- Recruited male and female probable AD (PRAD) patients and genotyped them for apoE epsilon3 and epsilon4 alleles.
- Quantified anxiety scores in PRAD patients based on their apoE genotype.
Main Results:
- Apoe-/- mice expressing human apoE4, but not apoE3, exhibited significantly increased measures of anxiety compared to wild-type controls.
- Apoe-/- mice lacking human apoE also showed heightened anxiety.
- Reduced microtubule-associated protein 2-positive neuronal dendrites were observed in the central nucleus of the amygdala in anxious mouse models.
- PRAD patients with the apoE epsilon4/epsilon4 genotype reported higher anxiety scores than those with the epsilon3/epsilon3 genotype.
Conclusions:
- Human apoE isoforms differentially modulate anxiety-related behaviors.
- The apoE4 isoform is associated with increased anxiety and specific neuroanatomical changes in the amygdala.
- These findings suggest a direct link between apoE genotype and anxiety in both AD mouse models and human AD patients.
