ArticleBMC genomics2016
A loss of function variant in CASP7 protects against Alzheimer's disease in homozygous APOE ε4 allele carriers.
Article in BMC genomics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 2 of them syntheses that pooled it.
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Who cites it
16 citing papers in PubMed, 2 syntheses or guidelines pooled it, 30 citations in OpenAlex.
- Transcriptional landscape of human microglia implicates age, sex, and APOE-related immunometabolic pathway perturbations.Aging cell · 2022Pooled it
- Genetic Variants Associated With Resilience in Human and Animal Studies.Frontiers in psychiatry · 2022Pooled it
- Protective mutations associated with APOE in Alzheimer's disease.Molecular psychiatry · 2026Review
- Genome-wide investigation of synthetic rescue interactions in Alzheimer's disease implicates glial lipid and sterol metabolism.Alzheimer's research & therapy · 2026Article
- Molecular Connections between DNA Replication and Cell Death in β-Amyloid-Treated Neurons.Current neuropharmacology · 2023Article
- Disclosure of Genetic Risk Factors for Alzheimer's Disease to Cognitively Healthy Individuals-From Current Practice towards a Personalised Medicine Scenario.Biomedicines · 2022Review
- Polygenic resilience scores capture protective genetic effects for Alzheimer's disease.Translational psychiatry · 2022Article
- Whole-genome sequencing reveals that variants in the Interleukin 18 Receptor Accessory Protein 3'UTR protect against ALS.Nature neuroscience · 2022Article
- Tau Protein Interaction Partners and Their Roles in Alzheimer's Disease and Other Tauopathies.International journal of molecular sciences · 2021Review
- How understudied populations have contributed to our understanding of Alzheimer's disease genetics.Brain : a journal of neurology · 2021Review
- Protective genes and pathways in Alzheimer's disease: moving towards precision interventions.Molecular neurodegeneration · 2021Review
- Polygenic risk score in postmortem diagnosed sporadic early-onset Alzheimer's disease.Neurobiology of aging · 2018Article
- Loss-of-function mutation inProceedings of the National Academy of Sciences of the United States of America · 2017Article
- The human-specific CASP4 gene product contributes to Alzheimer-related synaptic and behavioural deficits.Human molecular genetics · 2016Article
- VarI-SIG 2015: methods for personalized medicine - the role of variant interpretation in research and diagnostics.BMC genomics · 2016Article
- A modified Mediterranean-style diet enhances brain function via specific gut-microbiome-brain mechanisms.Gut microbesArticle
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundAlzheimer's disease (AD) represents the most common form of dementia in elder populations with approximately 30 million cases worldwide. Genome wide genotyping and sequencing studies have identified many genetic variants associated with late-onset Alzheimer's disease (LOAD). While most of these variants are associated with increased risk of developing LOAD, only limited number of reports focused on variants that are protective against the disease.
methodsHere we applied a novel approach to uncover protective alleles against AD by analyzing genetic and phenotypic data in Mount Sinai Biobank and Electronic Medical Record (EMR) databases.
resultsWe discovered a likely loss-of-function small deletion variant in the caspase 7 (CASP7) gene associated with significantly reduced incidence of LOAD in carriers of the high-risk APOE ε4 allele. Further investigation of four independent cohorts of European ancestry revealed the protective effect of the CASP7 variant against AD is most significant in homozygous APOE ε4 allele carriers. Meta analysis of multiple datasets shows overall odds ratio = 0.45 (p = 0.004). Analysis of RNA sequencing derived gene expression data indicated the variant correlates with reduced caspase 7 expression in multiple brain tissues we examined.
conclusionsTaken together, these results are consistent with the notion that caspase 7 plays a key role in microglial activation driving neuro-degeneration during AD pathogenesis, and may explain the underlying genetic mechanisms that anti-inflammatory interventions in AD show greater benefit in APOE ε4 carriers than non-carriers. Our findings inform potential novel therapeutic opportunities for AD and warrant further investigations.
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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.