ArticleAging cell2021
Synaptic dysregulation and hyperexcitability induced by intracellular amyloid beta oligomers.
Article in Aging cell, 2021. 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 26 papers.
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Who cites it
26 citing papers in PubMed, 35 citations in OpenAlex.
- Selective impairment of long-term depression in accumbal D1R+ MSNs involves calcium-permeable AMPARs in early Alzheimer's disease.Neurobiology of disease · 2026Article
- Parvalbumin interneurons in Alzheimer's disease: Physiological insights and pathophysiological mechanisms.Journal of cell communication and signaling · 2026Review
- PPT1 selectively depalmitoylates GAP43 to regulate neuronal excitability and cognitive function.Science advances · 2026Article
- Regional correlates of tau pathology and synaptic function in primary age-related tauopathy.Journal of Alzheimer's disease : JAD · 2026Article
- Selective impairment of long-term depression in accumbal D1-MSNs involves calcium-permeable AMPARs in Alzheimer's disease.bioRxiv : the preprint server for biology · 2026Article
- 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
- The interaction between neurotransmitter receptor activity and amyloid-β pathology in Alzheimer's disease.Journal of Alzheimer's disease : JAD · 2025Review
- Mechanisms of comorbidity between Alzheimer's disease and pain.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Review
- Neuron-Astrocyte Interactions in Aging and Alzheimer's Disease: Dysregulation of Amyloid Precursor Protein.Ageing & longevity · 2025Article
- Organelle perturbation in Alzheimer's disease: do intracellular amyloid-ß and the fragmented Golgi mediate early intracellular neurotoxicity?Frontiers in cell and developmental biology · 2025Review
- Quantitative Systems Pharmacology Development and Application in Neuroscience.Handbook of experimental pharmacology · 2025Review
- Adverse Effects of AβBiomolecules · 2024Article
- Neuronal connectivity, behavioral, and transcriptional alterations associated with the loss of MARK2.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2024Article
- Intermittent fasting and Alzheimer's disease-Targeting ketone bodies as a potential strategy for brain energy rescue.Metabolic brain disease · 2024Review
- Resveratrol Preconditioning Protects Against Ischemia-Induced Synaptic Dysfunction and Cofilin Hyperactivation in the Mouse Hippocampal Slice.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2023Article
- Exploring the Pathological Effect of Aβ42 Oligomers on Neural Networks in Primary Cortical Neuron Culture.International journal of molecular sciences · 2023Article
- Functional excitatory to inhibitory synaptic imbalance and loss of cognitive performance in people with Alzheimer's disease neuropathologic change.Acta neuropathologica · 2023Article
- Influence of amyloid beta on impulse spiking of isolated hippocampal neurons.Frontiers in cellular neuroscience · 2023Article
- The intracerebral injection of AβFrontiers in aging neuroscience · 2023Article
- Increased Heat Pain Tolerance but Hyperalgesia to Tonic Inflammatory Pain in the CRND8 Mouse Model of Alzheimer's Disease.Journal of Alzheimer's disease : JAD · 2023Article
Corrections and comments
- Erratum issued
Authors and funding
13 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Intracellular amyloid beta oligomer (iAβo) accumulation and neuronal hyperexcitability are two crucial events at early stages of Alzheimer's disease (AD). However, to date, no mechanism linking iAβo with an increase in neuronal excitability has been reported. Here, the effects of human AD brain-derived (h-iAβo) and synthetic (iAβo) peptides on synaptic currents and action potential firing were investigated in hippocampal neurons. Starting from 500 pM, iAβo rapidly increased the frequency of synaptic currents and higher concentrations potentiated the AMPA receptor-mediated current. Both effects were PKC-dependent. Parallel recordings of synaptic currents and nitric oxide (NO)-associated fluorescence showed that the increased frequency, related to pre-synaptic release, was dependent on a NO-mediated retrograde signaling. Moreover, increased synchronization in NO production was also observed in neurons neighboring those dialyzed with iAβo, indicating that iAβo can increase network excitability at a distance. Current-clamp recordings suggested that iAβo increased neuronal excitability via AMPA-driven synaptic activity without altering membrane intrinsic properties. These results strongly indicate that iAβo causes functional spreading of hyperexcitability through a synaptic-driven mechanism and offers an important neuropathological significance to intracellular species in the initial stages of AD, which include brain hyperexcitability and seizures.
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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.