ArticleEMBO reports2017
Posttranslational modification impact on the mechanism by which amyloid-β induces synaptic dysfunction.
Article in EMBO reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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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.
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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.
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Who cites it
36 citing papers in PubMed, 76 citations in OpenAlex.
- Safety, tolerability and efficacy of the glutaminyl cyclase inhibitor PQ912 in Alzheimer's disease: results of a randomized, double-blind, placebo-controlled phase 2a study.Alzheimer's research & therapy · 2018Trial
- High-Fat Diet and a High Amyloid Load Interact to Induce PKC-α Dependent Synaptic Insulin Resistance.Molecular & cellular proteomics : MCP · 2026Article
- Polarity-determined triple partition of dual binding pockets unlocks mechanistic insights and a novel antagonist design of NMDA receptors: a combined MD/DFT study.RSC advances · 2026Article
- Amyloid Beta in Alzheimer's Disease: Mechanisms, Biomarker Potential, and Therapeutic Targets.CNS neuroscience & therapeutics · 2025Review
- Effects of Dietary Vitamin D Levels on Markers Related to Amyloidogenesis and Neuroinflammation in db/db Mice.Nutrients · 2025Article
- Aggregation-Dependent Epitope Sequence and Modification Fingerprints of Anti-Aβ Antibodies.bioRxiv : the preprint server for biology · 2025Article
- Bridging prion biology and Alzheimer's disease: from pathogenic seeds to precision therapeutics.Frontiers in molecular neuroscience · 2025Review
- Protective effect of trehalose sugar on amyloid-membrane interactions using BLM electrophysiology.Biophysical journal · 2024Article
- Dual Role of NMDAR Containing NR2A and NR2B Subunits in Alzheimer's Disease.International journal of molecular sciences · 2024Article
- Associations of amyloid-β oligomers and plaques with neuropathology in theBrain communications · 2024Article
- Integration of nuclear CaCellular and molecular life sciences : CMLS · 2023Article
- Inhibition of Acetylcholinesterase and Amyloid-β Aggregation by Piceatannol and Analogs: Assessing In Vitro and In Vivo Impact on a Murine Model of Scopolamine-Induced Memory Impairment.Antioxidants (Basel, Switzerland) · 2023Article
- Novel Vaccine against Pathological Pyroglutamate-Modified Amyloid Beta for Prevention of Alzheimer's Disease.International journal of molecular sciences · 2023Article
- Jacob-induced transcriptional inactivation of CREB promotes Aβ-induced synapse loss in Alzheimer's disease.The EMBO journal · 2023Article
- Article
- Solid-phase synthesis and pathological evaluation of pyroglutamate amyloid-βScientific reports · 2023Article
- Development and evolution of human glutaminyl cyclase inhibitors (QCIs): an alternative promising approach for disease-modifying treatment of Alzheimer's disease.Frontiers in aging neuroscience · 2023Review
- Review
- Discovery of a novel pseudo β-hairpin structure of N-truncated amyloid-β for use as a vaccine against Alzheimer's disease.Molecular psychiatry · 2022Article
- Neddylation-dependent protein degradation is a nexus between synaptic insulin resistance, neuroinflammation and Alzheimer's disease.Translational neurodegeneration · 2022Article
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Oligomeric amyloid-β (Aβ) 1-42 disrupts synaptic function at an early stage of Alzheimer's disease (AD). Multiple posttranslational modifications of Aβ have been identified, among which N-terminally truncated forms are the most abundant. It is not clear, however, whether modified species can induce synaptic dysfunction on their own and how altered biochemical properties can contribute to the synaptotoxic mechanisms. Here, we show that a prominent isoform, pyroglutamated Aβ3(pE)-42, induces synaptic dysfunction to a similar extent like Aβ1-42 but by clearly different mechanisms. In contrast to Aβ1-42, Aβ3(pE)-42 does not directly associate with synaptic membranes or the prion protein but is instead taken up by astrocytes and potently induces glial release of the proinflammatory cytokine TNFα. Moreover, Aβ3(pE)-42-induced synaptic dysfunction is not related to NMDAR signalling and Aβ3(pE)-42-induced impairment of synaptic plasticity cannot be rescued by D1-agonists. Collectively, the data point to a scenario where neuroinflammatory processes together with direct synaptotoxic effects are caused by posttranslational modification of soluble oligomeric Aβ and contribute synergistically to the onset of synaptic dysfunction in AD.
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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.