ReviewMolecular neurodegeneration2019
Apolipoprotein E4, inhibitory network dysfunction, and Alzheimer's disease.
Review in Molecular neurodegeneration, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 106 papers, 3 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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Who cites it
106 citing papers in PubMed, 3 syntheses or guidelines pooled it, 190 citations in OpenAlex.
- Human induced pluripotent stem cell models for Alzheimer's disease research: a bibliometric analysis.Frontiers in human neuroscience · 2025Pooled it
- C/EBPβ: A transcription factor associated with the irreversible progression of Alzheimer's disease.CNS neuroscience & therapeutics · 2024Pooled it
- Olfactory dysfunction in aging and neurodegenerative diseases.Ageing research reviews · 2021Pooled it
- A compact GAD67 promoter enables inhibitory neuron-targeted AAV gene therapy for seizure suppression.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Review
- Investigation of the topological properties of brain structural and functional networks in patients with mild cognitive impairment.Quantitative imaging in medicine and surgery · 2026Article
- Increased alcohol drinking and seizure susceptibility in female humanized ApoE4 knockin rats.Physiology & behavior · 2026Article
- 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
- Plasma Proteomic Analysis ofmedRxiv : the preprint server for health sciences · 2026Article
- Article
- 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
- APOE4 reduces hippocampal expression of phosphoglycerate kinase 1 and sodium potassium pump to enhance seizure susceptibility in mice.Neurobiology of disease · 2026Article
- APOE4 and doxorubicin impair inhibitory interneuron function and homeostatic regulation in the entorhinal cortex.PloS one · 2026Article
- Stra8 links neuronal activity to inhibitory circuit protection in the adult mouse brain.Cell reports · 2025Article
- ACE2: Friend or Foe in Post-COVID-19 Neurodegeneration?International journal of molecular sciences · 2025Review
- Longitudinal functional connectivity during rest and task is differentially related to Alzheimer's pathology and episodic memory in older adults.Scientific reports · 2025Article
- Article
- APOE ε4 disrupts neuronal and network-level function in the anterior olfactory nucleus: Influence of age and sex.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Distinct gut microbiota profiles and network properties in older Korean individuals with subjective cognitive decline, mild cognitive impairment, and Alzheimer's disease.Alzheimer's research & therapy · 2025Article
46 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Apolipoprotein (apo) E4 is the major genetic risk factor for Alzheimer's disease (AD), increasing risk and decreasing age of disease onset. Many studies have demonstrated the detrimental effects of apoE4 in varying cellular contexts. However, the underlying mechanisms explaining how apoE4 leads to cognitive decline are not fully understood. Recently, the combination of human induced pluripotent stem cell (hiPSC) modeling of neurological diseases in vitro and electrophysiological studies in vivo have begun to unravel the intersection between apoE4, neuronal subtype dysfunction or loss, subsequent network deficits, and eventual cognitive decline. In this review, we provide an overview of the literature describing apoE4's detrimental effects in the central nervous system (CNS), specifically focusing on its contribution to neuronal subtype dysfunction or loss. We focus on γ-aminobutyric acid (GABA)-expressing interneurons in the hippocampus, which are selectively vulnerable to apoE4-mediated neurotoxicity. Additionally, we discuss the importance of the GABAergic inhibitory network to proper cognitive function and how dysfunction of this network manifests in AD. Finally, we examine how apoE4-mediated GABAergic interneuron loss can lead to inhibitory network deficits and how this deficit results in cognitive decline. We propose the following working model: Aging and/or stress induces neuronal expression of apoE. GABAergic interneurons are selectively vulnerable to intracellularly produced apoE4, through a tau dependent mechanism, which leads to their dysfunction and eventual death. In turn, GABAergic interneuron loss causes hyperexcitability and dysregulation of neural networks in the hippocampus and cortex. This dysfunction results in learning, memory, and other cognitive deficits that are the central features of AD.
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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.