ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2014
Apolipoprotein E4 produced in GABAergic interneurons causes learning and memory deficits in mice.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 71 papers.
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Who cites it
71 citing papers in PubMed, 93 citations in OpenAlex.
- Review
- APOE4 disrupts the central dogma by arresting neuronal proteome dynamics.bioRxiv : the preprint server for biology · 2026Article
- Cholesterol at the Center of Alzheimer's Disease: A Unifying Hypothesis on the Pathogenic Mechanism.Molecules (Basel, Switzerland) · 2026Review
- Exceptional Longevity Modifying Allele APOE2 Promotes DNA Signaling Pathways Resisting Cellular Senescence in Human Neurons.Aging cell · 2026Article
- Neuronal APOE4-induced early hippocampal network hyperexcitability in Alzheimer's disease pathogenesis.Nature aging · 2026Article
- Introducing the SAGE study: a multimodal protocol for testing a GABAergic mechanism of age-related episodic memory impairment across the sexes.BMJ neurology open · 2026Article
- ApoE expression across the CNS: Who, What, Where, When, and How (much)?Molecular neurodegeneration advances · 2026Review
- Neuronal APOE4 drives damaging lipid accumulation via contact-dependent neuron-oligodendrocyte-microglia interaction in Alzheimer's disease.bioRxiv : the preprint server for biology · 2025Article
- Lysosomal proteomics reveals mechanisms of neuronal APOE4-associated lysosomal dysfunction.Autophagy · 2025Article
- Neuronal APOE4 alone is sufficient to drive tau pathology, neurodegeneration, and neuroinflammation in an Alzheimer's disease mouse model.bioRxiv : the preprint server for biology · 2025Article
- Aging, Rather than Genotype, Is the Principal Contributor to Differential Gene Expression Within Targeted Replacement APOE2, APOE3, and APOE4 Mouse Brain.Brain sciences · 2025Article
- APOE4 impacts cortical neurodevelopment and alters network formation in human brain organoids.Stem cell reports · 2025Article
- Apolipoprotein E ε4-Specific Relationship Between Serum Olfactomedin 4 and Alzheimer's Disease.Molecular neurobiology · 2025Article
- Lysosomal proteomics reveals mechanisms of neuronal apoE4-associated lysosomal dysfunction.bioRxiv : the preprint server for biology · 2025Article
- Regulation of GABAergic neurotransmission by purinergic receptors in brain physiology and disease.Purinergic signalling · 2025Review
- Stem Cell Interventions in the Treatment of Alzheimer's Disease.Current stem cell research & therapy · 2025Review
- Stimulation of Locus Ceruleus Inputs to the Prelimbic Cortex in Mice Induces Cell Type-Specific Expression of theeNeuro · 2024Article
- APOE from astrocytes restores Alzheimer's Aβ-pathology and DAM-like responses in APOE deficient microglia.EMBO molecular medicine · 2024Article
- Somatostatin: Linking Cognition and Alzheimer Disease to Therapeutic Targeting.Pharmacological reviews · 2024Review
- Stimulation of locus coeruleus inputs to the frontal cortex in mice induces cell type-specific expression of thebioRxiv : the preprint server for biology · 2024Article
11 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Apolipoprotein (apo) E4 is expressed in many types of brain cells, is associated with age-dependent decline of learning and memory in humans, and is the major genetic risk factor for AD. To determine whether the detrimental effects of apoE4 depend on its cellular sources, we generated human apoE knock-in mouse models in which the human APOE gene is conditionally deleted in astrocytes, neurons, or GABAergic interneurons. Here we report that deletion of apoE4 in astrocytes does not protect aged mice from apoE4-induced GABAergic interneuron loss and learning and memory deficits. In contrast, deletion of apoE4 in neurons does protect aged mice from both deficits. Furthermore, deletion of apoE4 in GABAergic interneurons is sufficient to gain similar protection. This study demonstrates a detrimental effect of endogenously produced apoE4 on GABAergic interneurons that leads to learning and memory deficits in mice and provides a novel target for drug development for AD related to apoE4.
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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.