ArticlePloS one2017
Caspase-8, association with Alzheimer's Disease and functional analysis of rare variants.
Article in PloS one, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
30 citing papers in PubMed, 49 citations in OpenAlex.
- Microglia-mediated synaptic pruning in neural circuit remodeling: multidimensional control in homeostasis and neuropathology.BMC medicine · 2026Review
- APP-C31 pathology as a target in neurodegenerative diseases.Journal of biomedical science · 2026Review
- Article
- Systems pharmacology and multi-scale mechanism of Enicostema axillare bioactives in treating Alzheimer disease.Inflammopharmacology · 2024Article
- Innate and adaptive immune abnormalities underlying autoimmune diseases: the genetic connections.Science China. Life sciences · 2023Review
- Apoptotic cell death in disease-Current understanding of the NCCD 2023.Cell death and differentiation · 2023Review
- Jia-Wei-Kai-Xin-San Treatment Alleviated Mild Cognitive Impairment through Anti-Inflammatory and Antiapoptotic Mechanisms in SAMP8 Mice.Mediators of inflammation · 2023Article
- Arc Regulates Transcription of Genes for Plasticity, Excitability and Alzheimer's Disease.Biomedicines · 2022Article
- SDGCCA: Supervised Deep Generalized Canonical Correlation Analysis for Multi-Omics Integration.Journal of computational biology : a journal of computational molecular cell biology · 2022Article
- Myeloid caspase-8 restricts RIPK3-dependent proinflammatory IL-1β production and CD4 T cell activation in autoimmune demyelination.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Review
- Autophagy and apoptosis cascade: which is more prominent in neuronal death?Cellular and molecular life sciences : CMLS · 2021Review
- TNF-mediated neuroinflammation is linked to neuronal necroptosis in Alzheimer's disease hippocampus.Acta neuropathologica communications · 2021Article
- Tau Protein Interaction Partners and Their Roles in Alzheimer's Disease and Other Tauopathies.International journal of molecular sciences · 2021Review
- Molecular Mechanism of Vitamin K2 Protection against Amyloid-β-Induced Cytotoxicity.Biomolecules · 2021Article
- Serum Glycoproteomics and Identification of Potential Mechanisms Underlying Alzheimer's Disease.Behavioural neurology · 2021Article
- Isoforsythiaside Attenuates Alzheimer's Disease via Regulating Mitochondrial Function Through the PI3K/AKT Pathway.International journal of molecular sciences · 2020Article
- Anti-Apoptotic Effects of Carotenoids in Neurodegeneration.Molecules (Basel, Switzerland) · 2020Review
- Integrative X-ray Structure and Molecular Modeling for the Rationalization of Procaspase-8 Inhibitor Potency and Selectivity.ACS chemical biology · 2020Article
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
22 authors at 11 institutions in 4 countries.
Funding
Abstract
The accumulation of amyloid beta (Aβ) peptide (Amyloid cascade hypothesis), an APP protein cleavage product, is a leading hypothesis in the etiology of Alzheimer's disease (AD). In order to identify additional AD risk genes, we performed targeted sequencing and rare variant burden association study for nine candidate genes involved in the amyloid metabolism in 1886 AD cases and 1700 controls. We identified a significant variant burden association for the gene encoding caspase-8, CASP8 (p = 8.6x10-5). For two CASP8 variants, p.K148R and p.I298V, the association remained significant in a combined sample of 10,820 cases and 8,881 controls. For both variants we performed bioinformatics structural, expression and enzymatic activity studies and obtained evidence for loss of function effects. In addition to their role in amyloid processing, caspase-8 and its downstream effector caspase-3 are involved in synaptic plasticity, learning, memory and control of microglia pro-inflammatory activation and associated neurotoxicity, indicating additional mechanisms that might contribute to AD. As caspase inhibition has been proposed as a mechanism for AD treatment, our finding that AD-associated CASP8 variants reduce caspase function calls for caution and is an impetus for further studies on the role of caspases in AD and other neurodegenerative diseases.
Indexed as
Identifiers
What OpenQuestion holds
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.