ArticleJCI insight2020
Identification of Alzheimer's disease-associated rare coding variants in the ECE2 gene.
Article in JCI insight, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 24 citations in OpenAlex.
- Mapping fatigue: discovering brain regions and genes linked to fatigue susceptibility.Journal of translational medicine · 2025Article
- The role of peripheral innate immune cells in Alzheimer's disease progression.Frontiers in immunology · 2025Review
- Pathology of Amyloid-β (Aβ) Peptide Peripheral Clearance in Alzheimer's Disease.International journal of molecular sciences · 2024Review
- SIL1 improves cognitive impairment in APP23/PS45 mice by regulating amyloid precursor protein processing and Aβ generation.Zoological research · 2024Article
- Amyloid Precursor Protein: A Regulatory Hub in Alzheimer's Disease.Aging and disease · 2024Review
- Alzheimer's Disease: Models and Molecular Mechanisms Informing Disease and Treatments.Bioengineering (Basel, Switzerland) · 2024Review
- Nascent Aβ42 Fibrillization in Synaptic Endosomes Precedes Plaque Formation in a Mouse Model of Alzheimer's-like β-Amyloidosis.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2023Article
- Functional genomics identify causal variant underlying the protective CTSH locus for Alzheimer's disease.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2023Article
- Contributions of rare and common variation to early-onset and atypical dementia risk.Cold Spring Harbor molecular case studies · 2023Article
- Functional variants identify sex-specific genes and pathways in Alzheimer's Disease.Nature communications · 2023Article
- Contributions of rare and common variation to early-onset and atypical dementia risk.medRxiv : the preprint server for health sciences · 2023Article
- Neuroimmune contributions to Alzheimer's disease: a focus on human data.Molecular psychiatry · 2022Review
- Brain-derived neurotrophic factor in Alzheimer's disease and its pharmaceutical potential.Translational neurodegeneration · 2022Review
- ECE2 is a prognostic biomarker associated with m6A modification and involved in immune infiltration of lung adenocarcinoma.Frontiers in endocrinology · 2022Article
- Targeting Endothelin in Alzheimer's Disease: A Promising Therapeutic Approach.BioMed research international · 2021Review
- Bushen Huoxue Acupuncture Inhibits NLRP1 Inflammasome-Mediated Neuronal Pyroptosis in SAMP8 Mouse Model of Alzheimer's Disease.Neuropsychiatric disease and treatment · 2021Article
- Association of Genes Involved in the Metabolic Pathways of Amyloid-β and Tau Proteins With Sporadic Late-Onset Alzheimer's Disease in the Southern Han Chinese Population.Frontiers in aging neuroscience · 2020Article
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Authors and funding
19 authors at 3 institutions in 3 countries.
Funding
Abstract
Accumulation of amyloid β protein (Aβ) due to increased generation and/or impaired degradation plays an important role in Alzheimer's disease (AD) pathogenesis. In this report, we describe the identification of rare coding mutations in the endothelin-converting enzyme 2 (ECE2) gene in 1 late-onset AD family, and additional case-control cohort analysis indicates ECE2 variants associated with the risk of developing AD. The 2 mutations (R186C and F751S) located in the peptidase domain in the ECE2 protein were found to severely impair the enzymatic activity of ECE2 in Aβ degradation. We further evaluated the effect of the R186C mutation in mutant APP-knockin mice. Overexpression of wild-type ECE2 in the hippocampus reduced amyloid load and plaque formation, and improved learning and memory deficits in the AD model mice. However, the effect was abolished by the R186C mutation in ECE2. Taken together, the results demonstrated that ECE2 peptidase mutations contribute to AD pathogenesis by impairing Aβ degradation, and overexpression of ECE2 alleviates AD phenotypes. This study indicates that ECE2 is a risk gene for AD development and pharmacological activation of ECE2 could be a promising strategy for AD treatment.
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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 Socratic graph.