ArticleNature communications2017
Neuronal hyperactivity due to loss of inhibitory tone in APOE4 mice lacking Alzheimer's disease-like pathology.
Article in Nature communications, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04185298 (Mobile Technology-Based Simultaneous Aerobic Exercise and Memory Training Intervention for Older Adults With Mild Cognitive Impairment), which is not on this map. Cited by 120 papers, 1 of them a synthesis 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
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Mobile Technology-Based Simultaneous Aerobic Exercise and Memory Training Intervention for Older Adults With Mild Cognitive Impairment
Who cites it
120 citing papers in PubMed, 1 synthesis or guideline pooled it, 193 citations in OpenAlex.
- Finding memo: versatile interactions of the VPS10p-Domain receptors in Alzheimer's disease.Molecular neurodegeneration · 2022Pooled it
- Riluzole, a glutamate modulator, slows cerebral glucose metabolism decline in patients with Alzheimer's disease.Brain : a journal of neurology · 2021Trial
- Input-output curves demonstrate motor cortex hyperexcitability associated with cognitive impairment in Alzheimer's disease.Neurobiology of aging · 2026Article
- Fibronectin mediates APOE4-driven blood-brain barrier dysfunction in Alzheimer's disease.Nature aging · 2026Article
- Review
- Medial entorhinal-hippocampal desynchronization parallels the emergence of memory impairment in a mouse model of Alzheimer's disease pathology.Cell reports · 2026Article
- Subtyping and staging of Alzheimer's disease from routine structural MRI with PHASE-AD.medRxiv : the preprint server for health sciences · 2026Article
- Loss of endogenous tau suppresses APOE4-induced patterned behavioral decline and axon dysmorphia in a model of Alzheimer's disease.Disease models & mechanisms · 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
- A ketogenic diet improves memory in females in the APOE4 mouse model of Alzheimer's disease.GeroScience · 2026Article
- Transplantation of GABAergic Interneuron Progenitors Restores Cortical Circuit Function in an Alzheimer's Disease Mouse Model.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Excitation-inhibition homeostasis in Alzheimer's disease: a selective multiscale review of mechanisms, sex differences, and therapeutic opportunities.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Review
- APOE4 and doxorubicin impair inhibitory interneuron function and homeostatic regulation in the entorhinal cortex.PloS one · 2026Article
- APOE4 reduces hippocampal expression of phosphoglycerate kinase 1 and sodium potassium pump to enhance seizure susceptibility in mice.Neurobiology of disease · 2026Article
- A locus coeruleus-centric framework for novelty, salience, and gamma oscillations: implications for neurostimulation, aging, and disease.Frontiers in aging neuroscience · 2026Article
- Exploratory associations between APOE-εFrontiers in neurology · 2026Article
- 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
- GABAergic interneurons contribute to the fatal seizure phenotype of CLN2 disease mice.JCI insight · 2025Article
- 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
60 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
20 authors at 3 institutions in 1 country.
Funding
Abstract
The ε4 allele of apolipoprotein E (APOE) is the dominant genetic risk factor for late-onset Alzheimer's disease (AD). However, the reason APOE4 is associated with increased AD risk remains a source of debate. Neuronal hyperactivity is an early phenotype in both AD mouse models and in human AD, which may play a direct role in the pathogenesis of the disease. Here, we have identified an APOE4-associated hyperactivity phenotype in the brains of aged APOE mice using four complimentary techniques-fMRI, in vitro electrophysiology, in vivo electrophysiology, and metabolomics-with the most prominent hyperactivity occurring in the entorhinal cortex. Further analysis revealed that this neuronal hyperactivity is driven by decreased background inhibition caused by reduced responsiveness of excitatory neurons to GABAergic inhibitory inputs. Given the observations of neuronal hyperactivity in prodromal AD, we propose that this APOE4-driven hyperactivity may be a causative factor driving increased risk of AD among APOE4 carriers.
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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.