ArticleThe Journal of biological chemistry2014
Cognitive deficits and disruption of neurogenesis in a mouse model of apolipoprotein E4 domain interaction.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 43 citations in OpenAlex.
- Alzheimer's Disease Risk Factor APOE4 Exerts Dimorphic Effects on Female Bone.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Apolipoprotein E in Alzheimer's Disease: Focus on Synaptic Function and Therapeutic Strategy.Molecular neurobiology · 2025Review
- Sex-specific influences of APOEε4 genotype on hippocampal neurogenesis and progenitor cells in middle-aged rats.Biology of sex differences · 2025Article
- Black Seed Oil-Based Curcumin Nanoformulations Ameliorated Cuprizone-Induced Demyelination in the Mouse Hippocampus.Molecular neurobiology · 2025Article
- Age-dependent impairment of dopamine D1 receptor signalling in mouse striatum byBrain communications · 2025Article
- Curcumin-piperine nanoparticles mitigate cuprizone-induced cognitive impairment via antioxidant and anti-inflammatory mechanisms.Frontiers in nutrition · 2025Article
- Article
- Biochanin A Improves Memory Decline and Brain Pathology in Cuprizone-Induced Mouse Model of Multiple Sclerosis.Behavioral sciences (Basel, Switzerland) · 2022Article
- Adult Hippocampal Neurogenesis in Alzheimer's Disease: An Overview of Human and Animal Studies with Implications for Therapeutic Perspectives Aimed at Memory Recovery.Neural plasticity · 2022Review
- Ucp2-dependent microglia-neuronal coupling controls ventral hippocampal circuit function and anxiety-like behavior.Molecular psychiatry · 2021Article
- Familial Alzheimer's Disease Mutations in PSEN1 Lead to Premature Human Stem Cell Neurogenesis.Cell reports · 2021Article
- Deltamethrin Exposure Inhibits Adult Hippocampal Neurogenesis and Causes Deficits in Learning and Memory in Mice.Toxicological sciences : an official journal of the Society of Toxicology · 2020Article
- Chronic polypharmacy impairs explorative behavior and reduces synaptic functions in young adult mice.Aging · 2020Article
- Metabolic correlates of prevalent mild cognitive impairment and Alzheimer's disease in adults with Down syndrome.Alzheimer's & dementia (Amsterdam, Netherlands) · 2020Article
- Female mice with apolipoprotein E4 domain interaction demonstrated impairments in spatial learning and memory performance and disruption of hippocampal cyto-architecture.Neurobiology of learning and memory · 2019Article
- Humanising the mouse genome piece by piece.Nature communications · 2019Review
- REST and Neural Gene Network Dysregulation in iPSC Models of Alzheimer's Disease.Cell reports · 2019Article
- Human LRRK2 G2019S mutation represses post-synaptic protein PSD95 and causes cognitive impairment in transgenic mice.Neurobiology of learning and memory · 2017Article
- Molecular indicators of stress-induced neuroinflammation in a mouse model simulating features of post-traumatic stress disorder.Translational psychiatry · 2017Article
- Combination treatment with leptin and pioglitazone in a mouse model of Alzheimer's disease.Alzheimer's & dementia (New York, N. Y.) · 2017Article
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Apolipoprotein E4 (apoE4) allele is the major genetic risk factor for sporadic Alzheimer disease (AD) due to the higher prevalence and earlier onset of AD in apoE4 carriers. Accumulating data suggest that the interaction between the N- and the C-terminal domains in the protein may be the main pathologic feature of apoE4. To test this hypothesis, we used Arg-61 mice, a model of apoE4 domain interaction, by introducing the domain interaction feature of human apoE4 into native mouse apoE. We carried out hippocampus-dependent learning and memory tests and related cellular and molecular assays on 12- and 3-month-old Arg-61 and age-matched background C57BL/6J mice. Learning and memory task performance were impaired in Arg-61 mice at both old and young ages compared with C57BL/6J mice. Surprisingly, young Arg-61 mice had more mitotic doublecortin-positive cells in the subgranular zone; mRNA levels of brain-derived neurotrophic factor (BDNF) and TrkB were also higher in 3-month-old Arg-61 hippocampus compared with C57BL/6J mice. These early-age neurotrophic and neurogenic (proliferative) effects in the Arg-61 mouse may be an inadequate compensatory but eventually detrimental attempt by the system to "repair" itself. This is supported by the higher cleaved caspase-3 levels in the young animals that not only persisted, but increased in old age, and the lower levels of doublecortin at old age in the hippocampus of Arg-61 mice. These results are consistent with human apoE4-dependent cognitive and neuro-pathologic changes, supporting the principal role of domain interaction in the pathologic effect of apoE4. Domain interaction is, therefore, a viable therapeutic/prophylactic target for cognitive impairment and AD in apoE4 subjects.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.