ArticleAlzheimer's & dementia : the journal of the Alzheimer's Association2024
Synaptic and extrasynaptic distribution of NMDA receptors in the cortex of Alzheimer's disease patients.
Article in Alzheimer's & dementia : the journal of the Alzheimer's Association, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 1 of them a synthesis that pooled it.
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Who cites it
22 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Cost-effectiveness of testing biofluid biomarkers to diagnose Alzheimer's disease: a systematic review.The European journal of health economics : HEPAC : health economics in prevention and care · 2026Pooled it
- Systemic delivery of synapsin-promoted caveolin-1 overexpression ameliorates pathological TDP-43-induced cognitive decline and neurodegenerative changes.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Neurotransmitter Systems in Alzheimer's Disease.Current issues in molecular biology · 2026Review
- Alzheimer's disease and memantine effects on NMDA-receptor blockade: non-invasive in vivo insights from magnetoencephalography.Molecular psychiatry · 2026Article
- GluN2A-mediated currents and calcium signal in human iPSC-derived neurons.Scientific reports · 2026Article
- Automated ROI detection allows rapid quantification of synaptic activity across tens of thousands of synapses in cell culture.Frontiers in synaptic neuroscience · 2026Article
- Deciphering the Multi-Target Therapeutic Mechanisms of Traditional Chinese Medicine Against Alzheimer's Disease: A Network Pharmacology Perspective.Drug design, development and therapy · 2026Review
- New advances in small molecule drugs targeting NMDA receptors.Acta pharmacologica Sinica · 2026Review
- Inhba, Homer1 and Bdnf are major targets of transcriptomic dysregulation by neurodegenerative disease-associated excitotoxic NMDA receptor signaling.Communications biology · 2025Article
- The GluN3-containing NMDA receptors.Channels (Austin, Tex.) · 2025Review
- Multiple Roles for Neuregulins and Their v-Erb-B2 Avian Erythroblastic Leukemia Viral Oncogene Homolog Receptors in Neurodegenerative Disease Pathogenesis and Therapy.The American journal of pathology · 2025Review
- Glia inflammation and cell death pathways drive disease progression in preclinical and early AD.EMBO molecular medicine · 2025Article
- Differences in inflammatory markers, mitochondrial function, and synaptic proteins in male and female Alzheimer's disease post mortem brains.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Alterations of NMDAR Subunits in the Cerebrospinal Fluid Across Neurodegenerative and Immunological Disorders.Journal of neurochemistry · 2025Article
- Role of Ion Channels in Alzheimer's Disease Pathophysiology.The Journal of membrane biology · 2025Review
- Investigating the Impact of NMDA Receptor Organization and Biological Sex in the APPswe/PS1dE9 Mouse Model of Alzheimer's Disease.International journal of molecular sciences · 2025Article
- Future Perspectives of NMDAR in CNS Disorders.Molecules (Basel, Switzerland) · 2025Review
- NMDA receptors in neurodegenerative diseases: mechanisms and emerging therapeutic strategies.Frontiers in aging neuroscience · 2025Review
- Dysregulated calcium signaling in the aged primate association cortices: vulnerability to Alzheimer's disease neuropathology.Frontiers in aging neuroscience · 2025Review
- Contrasting patterns of extrasynaptic NMDAR-GluN2B expression in macaque subgenual cingulate and dorsolateral prefrontal cortices.Frontiers in neuroanatomy · 2025Article
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Abstract
backgroundSynaptic and extrasynaptic distribution of N-methyl-D-aspartate receptors (NMDARs) has not been addressed in the brain from Alzheimer´s disease (AD) subjects, despite their contribution to neurodegeneration.
methodsWe have developed a protocol to isolate synaptic and extrasynaptic membranes from controls and AD frontal cortex. We characterized the distribution of the NMDAR subunits GluN2B, GluN2A, GluN1, and GluN3A, as well as post-translational modifications, such as phosphorylation and glycosylation.
resultsLower levels of synaptic GluN2B and GluN2A were found in AD fractions, while extrasynaptic GluN2B and GluN1 levels were significantly higher; GluN3A distribution remained unaffected in AD. We also identified different glycoforms of GluN2B and GluN2A in extrasynaptic membranes. Synaptic Tyr1472 GluN2B phosphorylation was significantly lower in AD fractions. DISCUSSION: Reduction of synaptic NMDAR subunits, particularly for GluN2B, is likely to contribute to synaptic transmission failure in AD. Additionally, the increment of extrasynaptic NMDAR subunits could favor the activation of excitotoxicity in AD. HIGHLIGHTS: New protocol to isolate synaptic and extrasynaptic membranes from the human cortex. Low GluN2B and GluN2A levels in Alzheimer´s disease (AD) synaptic membranes. High GluN2B and GluN1 levels in AD extrasynaptic membranes. Specific glycoforms of extrasynaptic GluN2B and GluN2A. Low phosphorylation at Tyr1472 in synaptic GluN2B in AD.
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