Isabelle Quadrio1,2,3, Jean-Michel Dorey4,5, Jean Escal1,2, Anthony Fourier6,7, Maité Formaglio8,3, Luc Zimmer2, Emilien Bernard9,10, Hélène Mollion8,3, Muriel Bost1, Mathieu Herrmann4, Elisabeth Ollagnon-Roman11. 1. Laboratory of Neurobiology and Neurogenetics, Department of Biochemistry and Molecular Biology, Lyon University Hospital, Bron, France. 2. BIORAN Team, Lyon Neuroscience Research Center, CNRS UMR 5292, INSERM U1028, Lyon 1 University, Bron, France. 3. Center for Memory Resources and Research, Lyon University Hospital, Lyon 1 University, Villeurbanne, France. 4. Department of Aging Psychiatry, Hospital Le Vinatier, Bron, France. 5. Brain Dynamics and Cognition Team, Lyon Neuroscience Research Center, CNRS UMR 5292, INSERM U1028, Lyon, France. 6. Laboratory of Neurobiology and Neurogenetics, Department of Biochemistry and Molecular Biology, Lyon University Hospital, Bron, France. anthony.fourier@chu-lyon.fr. 7. BIORAN Team, Lyon Neuroscience Research Center, CNRS UMR 5292, INSERM U1028, Lyon 1 University, Bron, France. anthony.fourier@chu-lyon.fr. 8. Neurocognition and Neuro-Ophthalmology Department, Lyon University Hospital, Bron, France. 9. Reference Center of ALS of Lyon, Lyon University Hospital, Lyon 1 University, Bron, France. 10. NeuroMyoGène Institute, CNRS UMR 5310, INSERM U1217, Lyon 1 University, Lyon, France. 11. Department of Predictive Medicine of Neurological and Neurodegenerative Diseases, Lyon University Hospital, Lyon, France.
Abstract
OBJECTIVE: The 'Frontotemporal dementia-Amyotrophic lateral sclerosis Spectrum' (FAS) encompasses different phenotypes, including cognitive disorders (frontotemporal dementia, FTD) and/or motor impairments (amyotrophic lateral sclerosis, ALS). The aim of this study was to apprehend the specific uses of neurofilaments light chain (NfL) and phosphorylated neurofilaments heavy chain (pNfH) in a context of FAS. METHODS: First, NfL and pNfH were measured in 39 paired cerebrospinal fluid (CSF) and plasma samples of FAS and primary psychiatric disorders (PPD) patients, considered as controls. Secondly, additional plasma samples were included to examine a larger cohort of 81 samples composed of symptomatic FAS and PPD patients, presymptomatic and non-carrier relatives individuals. The measures were performed using Simoa technology. RESULTS: There was a positive correlation between CSF and plasma values for NfL (p < 0.0001) and for pNfH (p = 0.0036). NfL values were higher for all phenotypes of symptomatic FAS patients compared to PPD patients (p = 0.0016 in CSF; p = 0.0003 in plasma). On the contrary, pNfH values were solely increased in FAS patients exhibiting motor impairment. Unlike symptomatic FAS patients, presymptomatic cases had comparable concentrations with non-carrier individuals. CONCLUSION: NfL, but not pNfH, appeared to be useful in a context of differential diagnosis between FTD and psychiatric patients. Nevertheless, pNfH seem more specific for the diagnosis and follow-up of motor impairments. In each specific indication, measures in CSF and plasma will provide identical interpretations.
OBJECTIVE: The 'Frontotemporal dementia-Amyotrophic lateral sclerosis Spectrum' (FAS) encompasses different phenotypes, including cognitive disorders (frontotemporal dementia, FTD) and/or motor impairments (amyotrophic lateral sclerosis, ALS). The aim of this study was to apprehend the specific uses of neurofilaments light chain (NfL) and phosphorylated neurofilaments heavy chain (pNfH) in a context of FAS. METHODS: First, NfL and pNfH were measured in 39 paired cerebrospinal fluid (CSF) and plasma samples of FAS and primary psychiatric disorders (PPD) patients, considered as controls. Secondly, additional plasma samples were included to examine a larger cohort of 81 samples composed of symptomatic FAS and PPD patients, presymptomatic and non-carrier relatives individuals. The measures were performed using Simoa technology. RESULTS: There was a positive correlation between CSF and plasma values for NfL (p < 0.0001) and for pNfH (p = 0.0036). NfL values were higher for all phenotypes of symptomatic FAS patients compared to PPD patients (p = 0.0016 in CSF; p = 0.0003 in plasma). On the contrary, pNfH values were solely increased in FAS patients exhibiting motor impairment. Unlike symptomatic FAS patients, presymptomatic cases had comparable concentrations with non-carrier individuals. CONCLUSION: NfL, but not pNfH, appeared to be useful in a context of differential diagnosis between FTD and psychiatric patients. Nevertheless, pNfH seem more specific for the diagnosis and follow-up of motor impairments. In each specific indication, measures in CSF and plasma will provide identical interpretations.
Authors: Josh D Woolley; Baber K Khan; Nikhil K Murthy; Bruce L Miller; Katherine P Rankin Journal: J Clin Psychiatry Date: 2011-02 Impact factor: 4.384
Authors: Shunichiro Shinagawa; Joseree Ann Catindig; Nikolas R Block; Bruce L Miller; Katherine P Rankin Journal: Dement Geriatr Cogn Disord Date: 2016-01-08 Impact factor: 2.959
Authors: D De Silva; S Hsieh; J Caga; F V C Leslie; M C Kiernan; J R Hodges; E Mioshi; J R Burrell Journal: Acta Neurol Scand Date: 2015-07-30 Impact factor: 3.209
Authors: Harri Sivasathiaseelan; Charles R Marshall; Jennifer L Agustus; Elia Benhamou; Rebecca L Bond; Janneke E P van Leeuwen; Chris J D Hardy; Jonathan D Rohrer; Jason D Warren Journal: Semin Neurol Date: 2019-03-29 Impact factor: 3.420
Authors: Katya Rascovsky; John R Hodges; David Knopman; Mario F Mendez; Joel H Kramer; John Neuhaus; John C van Swieten; Harro Seelaar; Elise G P Dopper; Chiadi U Onyike; Argye E Hillis; Keith A Josephs; Bradley F Boeve; Andrew Kertesz; William W Seeley; Katherine P Rankin; Julene K Johnson; Maria-Luisa Gorno-Tempini; Howard Rosen; Caroline E Prioleau-Latham; Albert Lee; Christopher M Kipps; Patricia Lillo; Olivier Piguet; Jonathan D Rohrer; Martin N Rossor; Jason D Warren; Nick C Fox; Douglas Galasko; David P Salmon; Sandra E Black; Marsel Mesulam; Sandra Weintraub; Brad C Dickerson; Janine Diehl-Schmid; Florence Pasquier; Vincent Deramecourt; Florence Lebert; Yolande Pijnenburg; Tiffany W Chow; Facundo Manes; Jordan Grafman; Stefano F Cappa; Morris Freedman; Murray Grossman; Bruce L Miller Journal: Brain Date: 2011-08-02 Impact factor: 13.501
Authors: Rita Mejzini; Loren L Flynn; Ianthe L Pitout; Sue Fletcher; Steve D Wilton; P Anthony Akkari Journal: Front Neurosci Date: 2019-12-06 Impact factor: 4.677