ArticleActa neuropathologica2023
Functional excitatory to inhibitory synaptic imbalance and loss of cognitive performance in people with Alzheimer's disease neuropathologic change.
Article in Acta neuropathologica, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed, 62 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
- Efficacy and Safety of Jiannao Tongluo Granules in the Treatment of Convalescent Cerebral Infarction: A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Clinical Trial.Current medical science · 2026Article
- Multi-omics and electrophysiological examination of GABAMolecular psychiatry · 2026Article
- Early Retinal UCHL1 Dysregulation Coupled With Synaptic Loss Reflects Alzheimer's Disease Severity.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Drug screen and machine learning predict neuroprotective agents in a preclinical human model of childhood dementia.Nature communications · 2026Article
- Modelling synaptic dysfunction in childhood dementia using human iPSC-derived cortical networks.Nature communications · 2026Article
- 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
- Regional correlates of tau pathology and synaptic function in primary age-related tauopathy.Journal of Alzheimer's disease : JAD · 2026Article
- Selective vulnerability of human synapses to soluble tau oligomers.Journal of Alzheimer's disease : JAD · 2026Article
- Evidence for cPLA2 activation in Alzheimer's disease synaptic pathology.Acta neuropathologica communications · 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
- Excitation-inhibition homeostasis in Alzheimer's disease: a selective multiscale review of mechanisms, sex differences, and therapeutic opportunities.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Review
- Resting-State EEG Power and Aperiodic Activity in Individuals with Mild Cognitive Impairment and Cognitively Healthy Controls.Brain sciences · 2025Article
- Obesity and Cognitive Function: Leptin Role Through Blood-Brain Barrier and Hippocampus.Molecular neurobiology · 2025Review
- Decoding Alzheimer's Disease: Single-Cell Sequencing Uncovers Brain Cell Heterogeneity and Pathogenesis.Molecular neurobiology · 2025Review
- Molecular and neuropathological determinants of neuronal dysfunction in Alzheimer's disease.bioRxiv : the preprint server for biology · 2025Article
- MicroRNA-502-3p Modulates the GABA A Subunits, Synaptic Proteins, and Mitochondrial Morphology in Hippocampal Neurons.Molecular neurobiology · 2025Article
- Gene-Diet Interaction Analysis in UK Biobank Identified Genetic Loci That Modify the Association Between Fish Oil Supplementation and the Incidence of Dementia.Current developments in nutrition · 2025Article
- Executive dysfunction is associated with altered hippocampal-prefrontal functional connectivity in 3xTg Alzheimer's model mice.Communications biology · 2025Article
- A brain-derived tau oligomer polymorph is associated with cognitive resilience to Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
Abstract
Individuals at distinct stages of Alzheimer's disease (AD) show abnormal electroencephalographic activity, which has been linked to network hyperexcitability and cognitive decline. However, whether pro-excitatory changes at the synaptic level are observed in brain areas affected early in AD, and if they are emergent in MCI, is not clearly known. Equally important, it is not known whether global synaptic E/I imbalances correlate with the severity of cognitive impairment in the continuum of AD. Measuring the amplitude of ion currents of human excitatory and inhibitory synaptic receptors microtransplanted from the hippocampus and temporal cortex of cognitively normal, mildly cognitively impaired and AD individuals into surrogate cells, we found regional differences in pro-excitatory shifts of the excitatory to inhibitory (E/I) current ratio that correlates positively with toxic proteins and degree of pathology, and impinges negatively on cognitive performance scores. Using these data with electrophysiologically anchored analysis of the synapto-proteome in the same individuals, we identified a group of proteins sustaining synaptic function and those related to synaptic toxicity. We also found an uncoupling between the function and expression of proteins for GABAergic signaling in the temporal cortex underlying larger E/I and worse cognitive performance. Further analysis of transcriptomic and in situ hybridization datasets from an independent cohort across the continuum of AD confirm regional differences in pro-excitatory shifts of the E/I balance that correlate negatively with the most recent calibrated composite scores for memory, executive function, language and visuospatial abilities, as well as overall cognitive performance. These findings indicate that early shifts of E/I balance may contribute to loss of cognitive capabilities in the continuum of AD clinical syndrome.
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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.