ArticleProceedings of the National Academy of Sciences of the United States of America2013
Aβ induces astrocytic glutamate release, extrasynaptic NMDA receptor activation, and synaptic loss.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 359 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
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
359 citing papers in PubMed, 3 syntheses or guidelines pooled it, 581 citations in OpenAlex.
- Investigating the functional connectivity between central glucagon-like peptide-1 (GLP-1) and glutamatergic signaling: a systematic review.CNS spectrums · 2026Pooled it
- The Role of Astrocytes in Synapse Loss in Alzheimer's Disease: A Systematic Review.Frontiers in cellular neuroscience · 2022Pooled it
- Pooled it
- DTI-ALPS as a Biomarker of Small Vessel Disease Progression and Amyloid-β in Normal Aging: A 3-Year Longitudinal Study.Human brain mapping · 2026Article
- Ursolic acid reduces Aβ-driven aggression via Gab1-mediated autophagy and dorsal hippocampal circuit modulation in Alzheimer's disease.Journal of advanced research · 2026Article
- Functional and Transcriptional Downregulation of Glutamate Transporters (EAAT1 and EAAT2) via DNMT3B Overexpression in Glial Cells.Molecular neurobiology · 2026Article
- Memantine: updates from the past decade and implications for future novel therapeutic applications.Journal of neural transmission (Vienna, Austria : 1996) · 2026Review
- Impairment of hippocampal long-term potentiation by soluble amyloid-β oligomers is mediated by glutamate transporter 1 expressed in neurons.Neural regeneration research · 2026Article
- Localized amyloid-β oligomers in the lateral entorhinal cortex drives olfactory dysfunction through aberrant neuronal and network activity.Acta neuropathologica communications · 2026Article
- Article
- Glial Cells in Behavioral and Psychological Symptoms of Alzheimer's Disease.International journal of molecular sciences · 2026Review
- Astrocyte Proximity Protects Synapses From Human Amyloid-Beta Induced Degeneration in a Mouse Ex Vivo Model of Early Alzheimer's Disease.The European journal of neuroscience · 2026Article
- Toxic mechanisms of amyloid oligomers and therapeutic strategies.Protein science : a publication of the Protein Society · 2026Review
- How Do Amyloid Pathology and Aberrant Neuronal Activity Disrupt Plasticity and Memory in Alzheimer's Disease?The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry · 2026Review
- APOE-ε4 genotype and western diet synergistically aggravate synaptic dysfunction in Alzheimer's disease via D-serine disruption.Alzheimer's research & therapy · 2026Article
- Natural Anti-NMDAR1 autoantibodies associate with slowed decline of cognitive functions in Alzheimer's diseases.Translational psychiatry · 2026Article
- The NMDAR/TRPM4 death complex is a major promoter of disease progression in the 5xFAD mouse model of Alzheimer's disease.Molecular psychiatry · 2026Article
- Molecular mechanisms underlying exercise-enhanced autophagy in improving neuroplasticity in Alzheimer's disease.Frontiers in aging neuroscience · 2026Review
- Engram cell vulnerability in neurodegeneration: from mechanistic insights to therapeutic horizons.Frontiers in aging neuroscience · 2026Review
- The emerging role of astrocytes in spatial cognition, action and Alzheimer's disease.Frontiers in cellular neuroscience · 2026Review
299 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
- Erratum issued
- Erratum issued
Authors and funding
38 authors at 7 institutions in 3 countries.
Funding
Abstract
Synaptic loss is the cardinal feature linking neuropathology to cognitive decline in Alzheimer's disease (AD). However, the mechanism of synaptic damage remains incompletely understood. Here, using FRET-based glutamate sensor imaging, we show that amyloid-β peptide (Aβ) engages α7 nicotinic acetylcholine receptors to induce release of astrocytic glutamate, which in turn activates extrasynaptic NMDA receptors (eNMDARs) on neurons. In hippocampal autapses, this eNMDAR activity is followed by reduction in evoked and miniature excitatory postsynaptic currents (mEPSCs). Decreased mEPSC frequency may reflect early synaptic injury because of concurrent eNMDAR-mediated NO production, tau phosphorylation, and caspase-3 activation, each of which is implicated in spine loss. In hippocampal slices, oligomeric Aβ induces eNMDAR-mediated synaptic depression. In AD-transgenic mice compared with wild type, whole-cell recordings revealed excessive tonic eNMDAR activity accompanied by eNMDAR-sensitive loss of mEPSCs. Importantly, the improved NMDAR antagonist NitroMemantine, which selectively inhibits extrasynaptic over physiological synaptic NMDAR activity, protects synapses from Aβ-induced damage both in vitro and in vivo.
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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.