ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2014
Genetic suppression of transgenic APP rescues Hypersynchronous network activity in a mouse model of Alzeimer's disease.
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 97 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
97 citing papers in PubMed, 188 citations in OpenAlex.
- Spike-wave discharges are uncoupled with cognitive outcome in aged Long-Evans rats.Psychopharmacology · 2026Article
- Amyloid exacerbates tau and alpha-synuclein pathologies, behavioral impairments, and neuroinflammation in a mixed dementia model.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Impaired spatial coding and neuronal hyperactivity in the medial entorhinal cortex of aged APP knock-in mice.Cell reports · 2026Article
- The rise and deceleration of neuronal excitability in aging and Alzheimer's disease: Mechanisms, implications, and therapeutic targets.Ageing research reviews · 2026Review
- Altered patterning of neural activity in a neuropathology.Scientific reports · 2025Article
- The amyloid precursor family of proteins in excitatory neurons are essential for regulating cortico-hippocampal circuit dynamics in vivo.Cell reports · 2025Article
- Targeting high-affinity nicotinic receptors protects against the functional consequences of β-amyloid in mouse hippocampus.Molecular psychiatry · 2025Article
- A machine learning toolbox for the analysis of sharp-wave ripples reveals common waveform features across species.Communications biology · 2024Article
- Impairments of GABAergic transmission in hippocampus mediate increased susceptibility of epilepsy in the early stage of Alzheimer's disease.Cell communication and signaling : CCS · 2024Article
- Doxycycline for transgene control disrupts gut microbiome diversity without compromising acute neuroinflammatory response.Journal of neuroinflammation · 2024Article
- Transfixed by transgenics: how pathology assumptions are slowing progress in Alzheimer's disease and related dementia research.EMBO molecular medicine · 2023Article
- Bace1 Deletion in the Adult Reverses Epileptiform Activity and Sleep-wake Disturbances in AD Mice.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2023Article
- A machine learning toolbox for the analysis of sharp-wave ripples reveal common features across species.bioRxiv : the preprint server for biology · 2023Article
- Microglia specific deletion of miR-155 in Alzheimer's disease mouse models reduces amyloid-β pathology but causes hyperexcitability and seizures.Journal of neuroinflammation · 2023Article
- Knockdown of Amyloid Precursor Protein Increases Ion Channel Expression and Alters CaInternational journal of molecular sciences · 2023Article
- Microglial extracellular vesicles induce Alzheimer's disease-related cortico-hippocampal network dysfunction.Brain communications · 2023Article
- Clinical, imaging, and biomarker evidence of amyloid- and tau-related neurodegeneration in late-onset epilepsy of unknown etiology.Frontiers in neurology · 2023Review
- The intracerebral injection of AβFrontiers in aging neuroscience · 2023Article
- Novel App knock-in mouse model shows key features of amyloid pathology and reveals profound metabolic dysregulation of microglia.Molecular neurodegeneration · 2022Article
- Aβ/Amyloid Precursor Protein-Induced Hyperexcitability and Dysregulation of Homeostatic Synaptic Plasticity in Neuron Models of Alzheimer's Disease.Frontiers in aging neuroscience · 2022Article
37 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
13 authors at 7 institutions in 2 countries.
Funding
Abstract
Alzheimer's disease (AD) is associated with an elevated risk for seizures that may be fundamentally connected to cognitive dysfunction. Supporting this link, many mouse models for AD exhibit abnormal electroencephalogram (EEG) activity in addition to the expected neuropathology and cognitive deficits. Here, we used a controllable transgenic system to investigate how network changes develop and are maintained in a model characterized by amyloid β (Aβ) overproduction and progressive amyloid pathology. EEG recordings in tet-off mice overexpressing amyloid precursor protein (APP) from birth display frequent sharp wave discharges (SWDs). Unexpectedly, we found that withholding APP overexpression until adulthood substantially delayed the appearance of epileptiform activity. Together, these findings suggest that juvenile APP overexpression altered cortical development to favor synchronized firing. Regardless of the age at which EEG abnormalities appeared, the phenotype was dependent on continued APP overexpression and abated over several weeks once transgene expression was suppressed. Abnormal EEG discharges were independent of plaque load and could be extinguished without altering deposited amyloid. Selective reduction of Aβ with a γ-secretase inhibitor has no effect on the frequency of SWDs, indicating that another APP fragment or the full-length protein was likely responsible for maintaining EEG abnormalities. Moreover, transgene suppression normalized the ratio of excitatory to inhibitory innervation in the cortex, whereas secretase inhibition did not. Our results suggest that APP overexpression, and not Aβ overproduction, is responsible for EEG abnormalities in our transgenic mice and can be rescued independently of pathology.
Indexed as
Identifiers
What OpenQuestion holds
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.