ArticleActa neuropathologica2017
Conserved DNA methylation combined with differential frontal cortex and cerebellar expression distinguishes C9orf72-associated and sporadic ALS, and implicates SERPINA1 in disease.
Article in Acta neuropathologica, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 41 citations in OpenAlex.
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- Epigenetics in Neurodegenerative Diseases.Sub-cellular biochemistry · 2025Review
- Mapping the epigenomic landscape of post-traumatic stress disorder in human cortical neurons.medRxiv : the preprint server for health sciences · 2024Article
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- SerpinA1 levels in amyotrophic lateral sclerosis patients: An exploratory study.European journal of neurology · 2024Article
- Transcriptomics and Proteomics Approach for the Identification of Altered Blood microRNAs and Plasma Proteins in Parkinson's Disease.Cellular and molecular neurobiology · 2023Article
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- Immunosenescence: molecular mechanisms and diseases.Signal transduction and targeted therapy · 2023Review
- Discovery of Biomarkers for Amyotrophic Lateral Sclerosis from Human Cerebrospinal Fluid Using Mass-Spectrometry-Based Proteomics.Biomedicines · 2023Article
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- Multiregion transcriptomic profiling of the primate brain reveals signatures of aging and the social environment.Nature neuroscience · 2022Article
- Epigenetic Changes in Prion and Prion-like Neurodegenerative Diseases: Recent Advances, Potential as Biomarkers, and Future Perspectives.International journal of molecular sciences · 2022Review
- Hyperactivity of Purkinje cell and motor deficits in C9orf72 knockout mice.Molecular and cellular neurosciences · 2022Article
- Specific Cerebrospinal Fluid SerpinA1 Isoform Pattern in Alzheimer's Disease.International journal of molecular sciences · 2022Article
- Serpin Signatures in Prion and Alzheimer's Diseases.Molecular neurobiology · 2022Article
- Serpin neuropathology in the P497S UBQLN2 mouse model of ALS/FTD.Brain pathology (Zurich, Switzerland) · 2021Article
- Differential Epigenetic Signature of Corticospinal Motor Neurons in ALS.Brain sciences · 2021Article
- Repeat length increases disease penetrance and severity in C9orf72 ALS/FTD BAC transgenic mice.Human molecular genetics · 2021Article
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Authors and funding
19 authors at 2 institutions in 1 country.
Funding
Abstract
We previously found C9orf72-associated (c9ALS) and sporadic amyotrophic lateral sclerosis (sALS) brain transcriptomes comprise thousands of defects, among which, some are likely key contributors to ALS pathogenesis. We have now generated complementary methylome data and combine these two data sets to perform a comprehensive "multi-omic" analysis to clarify the molecular mechanisms initiating RNA misregulation in ALS. We found that c9ALS and sALS patients have generally distinct but overlapping methylome profiles, and that the c9ALS- and sALS-affected genes and pathways have similar biological functions, indicating conserved pathobiology in disease. Our results strongly implicate SERPINA1 in both C9orf72 repeat expansion carriers and non-carriers, where expression levels are greatly increased in both patient groups across the frontal cortex and cerebellum. SERPINA1 expression is particularly pronounced in C9orf72 repeat expansion carriers for both brain regions, where SERPINA1 levels are strictly down regulated across most human tissues, including the brain, except liver and blood, and are not measurable in E18 mouse brain. The altered biological networks we identified contain critical molecular players known to contribute to ALS pathology, which also interact with SERPINA1. Our comprehensive combined methylation and transcription study identifies new genes and highlights that direct genetic and epigenetic changes contribute to c9ALS and sALS pathogenesis.
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