Elevated Cerebrospinal Fluid Ubiquitin Carboxyl-Terminal Hydrolase Isozyme L1 in Asymptomatic C9orf72 Hexanucleotide Repeat Expansion Carriers.
| Autor: | Dellar ER; Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK., Vendrell I; Target Discovery Institute, Centre for Medicines Discovery, Nuffield Department of Medicine, University of Oxford, Oxford, UK.; Chinese Academy of Medical Science Oxford Institute, University of Oxford, Oxford, UK., Amein B; Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK., Lester DG; Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK., Edmond EC; Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK., Yoganathan K; Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK., Dharmadasa T; The Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, Victoria, Australia., Sogorb-Esteve A; Dementia Research Centre, Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, University College London, London, UK.; UK Dementia Research Institute at University College London, London, UK., Fischer R; Target Discovery Institute, Centre for Medicines Discovery, Nuffield Department of Medicine, University of Oxford, Oxford, UK.; Chinese Academy of Medical Science Oxford Institute, University of Oxford, Oxford, UK., Talbot K; Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK.; Kavli Institute for Nanoscience Discovery, University of Oxford, Oxford, UK., Rohrer JD; Dementia Research Centre, Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, University College London, London, UK., Turner MR; Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK., Thompson AG; Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK. |
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| Jazyk: | angličtina |
| Zdroj: | Annals of neurology [Ann Neurol] 2024 Nov 16. Date of Electronic Publication: 2024 Nov 16. |
| DOI: | 10.1002/ana.27133 |
| Abstrakt: | Objective: To identify biochemical changes in individuals at higher risk of developing amyotrophic lateral sclerosis (ALS) or frontotemporal dementia (FTD) via C9orf72 hexanucleotide repeat expansion (HRE) heterozygosity. Methods: Cross-sectional observational study of 48 asymptomatic C9orf72 HRE carriers, 39 asymptomatic non-carrier controls, 19 people with sporadic ALS, 10 with C9orf72 ALS, 14 with sporadic FTD, and 10 with C9orf72 FTD. Relative abundance of 30 pre-defined cerebrospinal fluid biomarkers of ALS and FTD were compared in asymptomatic C9orf72 HRE carriers and age-matched non-carrier controls. Differential abundance of these proteins was quantified using data independent acquisition mass spectrometry or electro chemiluminescent assay for neurofilament light chain. Unbiased analysis of the entire cerebrospinal fluid proteome was then carried out. Results: Ubiquitin carboxyl-hydrolase isozyme L1 levels were higher in asymptomatic C9orf72 HRE carriers compared with age-matched non-carriers (log Interpretation: Elevated cerebrospinal fluid ubiquitin carboxyl-hydrolase isozyme L1 levels in C9orf72 HRE carriers can occur in the absence of increased neurofilament levels, potentially reflecting either compensatory or pathogenic mechanisms preceding rapid neuronal loss. This brings forward the window on changes associated with the C9orf72 HRE carrier state, with potential to inform understanding of penetrance and approaches to prevention. ANN NEUROL 2024. (© 2024 The Author(s). Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.) |
| Databáze: | MEDLINE |
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