ArticleCerebral cortex (New York, N.Y. : 1991)2019
Aberrant Excitatory-Inhibitory Synaptic Mechanisms in Entorhinal Cortex Microcircuits During the Pathogenesis of Alzheimer's Disease.
Article in Cerebral cortex (New York, N.Y. : 1991), 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 76 papers, 1 of them a synthesis that pooled it.
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Who cites it
76 citing papers in PubMed, 1 synthesis or guideline pooled it, 132 citations in OpenAlex.
- Neuroinflammation: A Common Pathway in Alzheimer's Disease and Epilepsy.Journal of Alzheimer's disease : JAD · 2023Pooled it
- Medial entorhinal-hippocampal desynchronization parallels the emergence of memory impairment in a mouse model of Alzheimer's disease pathology.Cell reports · 2026Article
- Impaired spatial coding and neuronal hyperactivity in the medial entorhinal cortex of aged APP knock-in mice.Cell reports · 2026Article
- Localized amyloid-β oligomers in the lateral entorhinal cortex drives olfactory dysfunction through aberrant neuronal and network activity.Acta neuropathologica communications · 2026Article
- Prodromal changes in cortical neuron physiology before amyloid pathology in a mild model of Alzheimer's disease.Scientific reports · 2026Article
- Selective weakening of population-coupled synaptic activity in vivo in a mouse model of amyloid-beta pathology.Nature communications · 2026Article
- Methodology for human-induced pluripotent stem cell-derived excitatory and inhibitory neuron coculture with astrocytes for Alzheimer's disease modelling.Brain communications · 2026Article
- APOE4 and doxorubicin impair inhibitory interneuron function and homeostatic regulation in the entorhinal cortex.PloS one · 2026Article
- Review
- Tau conveys intrinsic hyperactivity of VTA dopamine neurons but an inability to sustain burst firing.bioRxiv : the preprint server for biology · 2025Article
- A central role for acetylcholine in entorhinal cortex function and dysfunction with age in humans and mice.Cell reports · 2025Article
- Revealing excitation-inhibition imbalance in Alzheimer's disease using multiscale neural model inversion of resting-state functional MRI.Communications medicine · 2025Article
- Hippocampal and cortical activities reflect early hyperexcitability in an Alzheimer's mouse model.Brain communications · 2025Article
- Excessive Alcohol Use as a Risk Factor for Alzheimer's Disease: Epidemiological and Preclinical Evidence.Advances in experimental medicine and biology · 2025Review
- Astrocyte-derived MFG-E8 facilitates microglial synapse elimination in Alzheimer's disease mouse models.bioRxiv : the preprint server for biology · 2024Article
- Cognitive resilience to Alzheimer's disease characterized by cell-type abundance.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Article
- Early hippocampal hyperexcitability and synaptic reorganization in mouse models of amyloidosis.iScience · 2024Article
- Entorhinal cortex vulnerability to human APP expression promotes hyperexcitability and tau pathology.Nature communications · 2024Article
- Advances in Therapeutics to Alleviate Cognitive Decline and Neuropsychiatric Symptoms of Alzheimer's Disease.International journal of molecular sciences · 2024Review
- Delineating mechanisms underlying parvalbumin neuron impairment in different neurological and neurodegenerative disorders: the emerging role of mitochondrial dysfunction.Biochemical Society transactions · 2024Review
16 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
Synaptic dysfunction is widely proposed as an initial insult leading to the neurodegeneration observed in Alzheimer's disease (AD). We hypothesize that the initial insult originates in the lateral entorhinal cortex (LEC) due to deficits in key interneuronal functions and synaptic signaling mechanisms, in particular, Wnt (Wingless/integrated). To investigate this hypothesis, we utilized the first knock-in mouse model of AD (AppNL-F/NL-F), expressing a mutant form of human amyloid-β (Aβ) precursor protein. This model shows an age-dependent accumulation of Aβ, neuroinflammation, and neurodegeneration. Prior to the typical AD pathology, we showed a decrease in canonical Wnt signaling activity first affecting the LEC in combination with synaptic hyperexcitation and severely disrupted excitatory-inhibitory inputs onto principal cells. This synaptic imbalance was consistent with a reduction in the number of parvalbumin-containing (PV) interneurons, and a reduction in the somatic inhibitory axon terminals in the LEC compared with other cortical regions. However, targeting GABAA receptors on PV cells using allosteric modulators, diazepam, zolpidem, or a nonbenzodiazepine, L-838,417 (modulator of α2/3 subunit-containing GABAA receptors), restored the excitatory-inhibitory imbalance observed at principal cells in the LEC. These data support our hypothesis, providing a rationale for targeting the synaptic imbalance in the LEC for early stage therapeutic intervention to prevent neurodegeneration in AD.
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