ArticleJournal of neurochemistry2022
Independent APOE4 knock-in mouse models display reduced brain APOE protein, altered neuroinflammation, and simplification of dendritic spines.
Article in Journal of neurochemistry, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 23 citations in OpenAlex.
- Article
- Gene therapy for liver diseases: methods, challenges and opportunities.Journal of nanobiotechnology · 2026Review
- Effect of High-Salt Diet on Memory and Behavior in Mice Expressing Human Apolipoprotein Epsilon-4 (APOE4) Allele.NeuroSci · 2026Article
- Molecular characterization of humanized APOE mouse models reveals source and genotype dependent differences.Molecular neurodegeneration · 2026Article
- Article
- APOE4 and doxorubicin impair inhibitory interneuron function and homeostatic regulation in the entorhinal cortex.PloS one · 2026Article
- ApoE expression across the CNS: Who, What, Where, When, and How (much)?Molecular neurodegeneration advances · 2026Review
- Humanized APOE mouse brain volume increases over age irrespective of sex and APOE genotype: implications for translational validity to the human.Frontiers in neuroscience · 2026Article
- Increased levels of HAPLN2, which anchors dense extracellular matrix, in the hippocampus of APOE4 targeted replacement mice.bioRxiv : the preprint server for biology · 2025Article
- Humanized APOE mouse brain volume increases over age irrespective of sex and APOE genotype: Implications for translational validity to the human.bioRxiv : the preprint server for biology · 2025Article
- APOE4 genotype and aging impair injury-induced microglial behavior in brain slices, including toward Aβ, through P2RY12.Molecular neurodegeneration · 2024Article
- Modeling sporadic Alzheimer's disease in mice by combining Apolipoprotein E4 risk gene with environmental risk factors.Frontiers in aging neuroscience · 2024Article
- Genome-wide analysis identifies novel loci influencing plasma apolipoprotein E concentration and Alzheimer's disease risk.Molecular psychiatry · 2023Article
- Astrocytic APOE4 genotype-mediated negative impacts on synaptic architecture in human pluripotent stem cell model.Stem cell reports · 2023Article
- The role of ApoE-mediated microglial lipid metabolism in brain aging and disease.Immunometabolism (Cobham, Surrey) · 2023Review
- Matrix disequilibrium in Alzheimer's disease and conditions that increase Alzheimer's disease risk.Frontiers in neuroscience · 2023Review
- Humanized APP is the primary determinant of regional brain volume in humanized APOE knock-in mice: a cross-sectional ex vivo MRI study.Alzheimer's & dementia (New York, N. Y.)Article
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5 authors at 1 institution in 1 country.
Funding
Abstract
APOE is an immunomodulator in the brain and the major genetic risk factor for late-onset Alzheimer's disease (AD). Targeted replacement APOE mice (APOE-TR) have been a useful tool to study the effects of APOE isoforms on brain neurochemistry and activity prior to and during AD. We use newly available APOE knock-in mice (JAX-APOE) to compare phenotypes associated with APOE4 across models. Similar to APOE4-TR mice, JAX-E4 mouse brains showed 27% lower levels of APOE protein compared with JAX-E3 (p < 0.001). We analyzed several neuroinflammatory molecules that have been associated with APOE genotype. SerpinA3 was much higher in APOE4-TR mice to APOE3-TR mice, but this effect was not seen in JAX-APOE mice. There were higher levels of IL-3 in JAX-E4 brains compared with JAX-E3, but other neuroinflammatory markers (IL6, TNFα) were not affected by APOE genotype. In terms of neuronal structure, basal dendritic spine density in the entorhinal cortex was 39% lower in JAX-E4 mice compared with JAX-E3 mice (p < 0.001), again similar to APOE-TR mice. One-week treatment with ibuprofen significantly increased dendritic spine density in the JAX-E4 mice, consistent with our previous finding in APOE-TR mice. Behaviorally, there was no effect of APOE genotype on Barnes Maze learning and memory in 6-month-old JAX-APOE mice. Overall, the experiments performed in JAX-APOE mice validated findings from APOE-TR mice, identifying particularly strong effects of APOE4 genotype on lower APOE protein levels and simplified neuron structure. These data demonstrate pathways that could promote susceptibility of APOE4 brains to AD pathological changes.
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