Elina Millere1,2, Dmitrijs Rots3, Joel Simrén4,5, Nicholas J Ashton4,5, Einars Kupats6, Ieva Micule7, Viktorija Priedite8, Natalja Kurjane9,10, Kaj Blennow4,5, Linda Gailite3, Henrik Zetterberg4,5,11,12, Viktorija Kenina9,13. 1. Department of Neurology and Neurosurgery, Children's Clinical University Hospital, Riga, Latvia. 2. Department of Doctoral Studies, Riga Stradins University, Riga, Latvia. 3. Scientific Laboratory of Molecular Genetics, Riga Stradins University, Riga, Latvia. 4. Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Mölndal, Sweden. 5. Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden. 6. Department of Neurology, Riga East Clinical University Hospital, Riga, Latvia. 7. Clinic of Medical Genetics and Prenatal Diagnostics, Children's Clinical University Hospital, Riga, Latvia. 8. BIOCON Laboratory, Riga, Latvia. 9. Department of Biology and Microbiology, Riga Stradins University, Riga, Latvia. 10. Outpatient Service Centre, Pauls Stradins Clinical University Hospital, Riga, Latvia. 11. Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, London, UK. 12. UK Dementia Research Institute, UCL, London, UK. 13. Rare Disease Centre, Riga East Clinical University Hospital, Riga, Latvia.
Abstract
BACKGROUND AND PURPOSE: Charcot-Marie-Tooth (CMT) disease is a chronic, slowly progressing disorder. The lack of specific disease progression biomarkers limits the execution of clinical trials. However, neurofilament light chain (NfL) has been suggested as a potential biomarker for peripheral nervous system disorders. METHODS: Ninety-six CMT disease patients and 60 healthy controls were enrolled in the study. Disease severity assessment included clinical evaluation with CMT Neuropathy Score version 2 (CMTNSv2). Blood plasma NfL concentrations were measured using the single-molecule array NfL assay. RESULTS: The NfL concentration was significantly higher in the CMT disease patient group than in the controls (p < 0.001). Of the CMT disease patients, those with type CMTX1 had a higher NfL level than those in the two other analysed subgroups (CMT1A and other CMT disease types) (p = 0.0498). The NfL concentration had a significant but weak correlation with the CMTNSv2 (rs = 0.25, p = 0.012). In one CMT disease patient with an extremely elevated NfL level, overlap with chronic inflammatory demyelinating polyneuropathy was suspected. Receiver operating characteristic analysis showed that an NfL concentration of 8.9 pg/ml could be used to discriminate CMT disease patients from controls, with an area under the curve of 0.881. CONCLUSIONS: Our study confirmed that the plasma NfL concentration is significantly higher in CMT disease patients than in controls. Plasma NfL concentration was found to significantly, albeit weakly, reflect the clinical severity of CMT disease. In the future, NfL may be used, either individually or collaboratively, as a biomarker in the clinical context of suspected CMT disease; however, several issues need to be addressed first.
BACKGROUND AND PURPOSE: Charcot-Marie-Tooth (CMT) disease is a chronic, slowly progressing disorder. The lack of specific disease progression biomarkers limits the execution of clinical trials. However, neurofilament light chain (NfL) has been suggested as a potential biomarker for peripheral nervous system disorders. METHODS: Ninety-six CMT disease patients and 60 healthy controls were enrolled in the study. Disease severity assessment included clinical evaluation with CMT Neuropathy Score version 2 (CMTNSv2). Blood plasma NfL concentrations were measured using the single-molecule array NfL assay. RESULTS: The NfL concentration was significantly higher in the CMT disease patient group than in the controls (p < 0.001). Of the CMT disease patients, those with type CMTX1 had a higher NfL level than those in the two other analysed subgroups (CMT1A and other CMT disease types) (p = 0.0498). The NfL concentration had a significant but weak correlation with the CMTNSv2 (rs = 0.25, p = 0.012). In one CMT disease patient with an extremely elevated NfL level, overlap with chronic inflammatory demyelinating polyneuropathy was suspected. Receiver operating characteristic analysis showed that an NfL concentration of 8.9 pg/ml could be used to discriminate CMT disease patients from controls, with an area under the curve of 0.881. CONCLUSIONS: Our study confirmed that the plasma NfL concentration is significantly higher in CMT disease patients than in controls. Plasma NfL concentration was found to significantly, albeit weakly, reflect the clinical severity of CMT disease. In the future, NfL may be used, either individually or collaboratively, as a biomarker in the clinical context of suspected CMT disease; however, several issues need to be addressed first.
Authors: Marina Stavrou; Alexia Kagiava; Sarah G Choudury; Matthew J Jennings; Lindsay M Wallace; Allison M Fowler; Amanda Heslegrave; Jan Richter; Christina Tryfonos; Christina Christodoulou; Henrik Zetterberg; Rita Horvath; Scott Q Harper; Kleopas A Kleopa Journal: J Clin Invest Date: 2022-07-01 Impact factor: 19.456
Authors: Jennifer A Frontera; Allal Boutajangout; Arjun V Masurkar; Rebecca A Betensky; Yulin Ge; Alok Vedvyas; Ludovic Debure; Andre Moreira; Ariane Lewis; Joshua Huang; Sujata Thawani; Laura Balcer; Steven Galetta; Thomas Wisniewski Journal: Alzheimers Dement Date: 2022-01-13 Impact factor: 16.655