ArticlePLoS genetics2015
Linking aβ42-induced hyperexcitability to neurodegeneration, learning and motor deficits, and a shorter lifespan in an Alzheimer's model.
Article in PLoS genetics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 63 citations in OpenAlex.
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- Understanding quantitative effects of anti-amyloid therapies on tau biomarkers and functional outcome. Insights from a comprehensive mechanistic quantitative systems pharmacology study.Frontiers in pharmacology · 2026Article
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- Intermittent Vibration Induces Sleep via an Allatostatin A-GABA Signaling Pathway and Provides Broad Benefits in Alzheimer's Disease Models.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Voltage Gated Ion Channels and Sleep.The Journal of membrane biology · 2024Review
- Modeling neurodegenerative and neurodevelopmental disorders in theLearning & memory (Cold Spring Harbor, N.Y.) · 2024Review
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- Latest advances in mechanisms of epileptic activity in Alzheimer's disease and dementia with Lewy Bodies.Frontiers in neurology · 2024Review
- Resveratrol and Sir2 Reverse Sleep and Memory Defects Induced by Amyloid Precursor Protein.Neuroscience bulletin · 2023Article
- Cerebral Semaphorin3D is a novel risk factor for age-associated cognitive impairment.Cell communication and signaling : CCS · 2023Article
- Ensheathing glia promote increased lifespan and healthy brain aging.Aging cell · 2023Article
- Influence of amyloid beta on impulse spiking of isolated hippocampal neurons.Frontiers in cellular neuroscience · 2023Article
- P. edulis Extract Protects Against Amyloid-β Toxicity in Alzheimer's Disease Models Through Maintenance of Mitochondrial Homeostasis via the FOXO3/DAF-16 Pathway.Molecular neurobiology · 2022Article
- DYRK1a Inhibitor Mediated Rescue ofFrontiers in pharmacology · 2022Article
- Slo2/KThe Journal of neuroscience : the official journal of the Society for Neuroscience · 2021Article
- Ergosta-7,9(11),22-trien-3β-ol Rescues AD Deficits by Modulating Microglia Activation but Not Oxidative Stress.Molecules (Basel, Switzerland) · 2021Article
- TPEN attenuates amyloid-βMolecular brain · 2021Article
- Differential gene expression in Drosophila melanogaster and D. nigrosparsa infected with the same Wolbachia strain.Scientific reports · 2021Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
Abstract
Alzheimer's disease (AD) is the most prevalent form of dementia in the elderly. β-amyloid (Aβ) accumulation in the brain is thought to be a primary event leading to eventual cognitive and motor dysfunction in AD. Aβ has been shown to promote neuronal hyperactivity, which is consistent with enhanced seizure activity in mouse models and AD patients. Little, however, is known about whether, and how, increased excitability contributes to downstream pathologies of AD. Here, we show that overexpression of human Aβ42 in a Drosophila model indeed induces increased neuronal activity. We found that the underlying mechanism involves the selective degradation of the A-type K+ channel, Kv4. An age-dependent loss of Kv4 leads to an increased probability of AP firing. Interestingly, we find that loss of Kv4 alone results in learning and locomotion defects, as well as a shortened lifespan. To test whether the Aβ42-induced increase in neuronal excitability contributes to, or exacerbates, downstream pathologies, we transgenically over-expressed Kv4 to near wild-type levels in Aβ42-expressing animals. We show that restoration of Kv4 attenuated age-dependent learning and locomotor deficits, slowed the onset of neurodegeneration, and partially rescued premature death seen in Aβ42-expressing animals. We conclude that Aβ42-induced hyperactivity plays a critical role in the age-dependent cognitive and motor decline of this Aβ42-Drosophila model, and possibly in 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.