January 02, 2018; 90 (1) Article
Multicenter evaluation of neurofilaments in early symptom onset amyotrophic lateral sclerosis
Emily Feneberg, Patrick Oeckl, Petra Steinacker, Federico Verde, Christian Barro, Philip Van Damme, Elizabeth Gray, Julian Grosskreutz, Claude Jardel, Jens Kuhle, Sonja Koerner, Foudil Lamari, Maria del Mar Amador, Benjamin Mayer, Claudia Morelli, Petra Muckova, Susanne Petri, Koen Poesen, Joost Raaphorst, François Salachas, Vincenzo Silani, Beatrice Stubendorff, Martin R. Turner, Marcel M. Verbeek, Jochen H. Weishaupt, Patrick Weydt, Albert C. Ludolph, Markus Otto
First published December 6, 2017, DOI: https://doi.org/10.1212/WNL.0000000000004761
Emily Feneberg
From the Nuffield Department of Clinical Neurosciences (E.F., E.G., M.R.T.), University of Oxford, UK; Department of Neurology (P.O., P.S., F.V., J.H.W., P.W., A.C.L., M.O.), Ulm University Hospital, Germany; Department of Pathophysiology and Transplantation (F.V., V.S.), Università degli Studi di Milano; Department of Neurology–Stroke Unit and Laboratory of Neuroscience (F.V., C.M., V.S.), IRCCS Istituto Auxologico Italiano, Milan, Italy; Neurologic Clinic and Policlinic, Departments of Medicine, Clinical Research, and Biomedicine (C.B., J.K.), University Hospital and University of Basel, Switzerland; Department of Neurology (P.V.D.) and Laboratory of Molecular Neurobiomarker Research and Laboratory Medicine (K.P.), University Hospitals Leuven; KU Leuven–University of Leuven (P.V.D.); Department of Neurosciences (P.V.D.), VIB–Center for Brain & Disease Research, Leuven, Belgium; Department of Neurology (J.G., P.M., B.S.), Jena University Hospital, Germany; Department of Metabolic Biochemistry (C.J., F.L.) and Neurological Diseases Department (M.d.M.A., F.S.), Hôpitaux Universitaires Pitié Salpêtrière–Charles Foix, Paris, France; Department of Neurology (S.K., S.P.), Hannover Medical School; Institute for Epidemiology and Medical Biometry (B.M.) Ulm University, Germany; Donders Institute for Brain, Cognition and Behaviour, Department of Neurology (J.R., M.M.V.), and Radboud Alzheimer Center, Department of Laboratory Medicine (M.M.V.), Radboud University Medical Center, Nijmegen, the Netherlands; and Department of Neurodegenerative Disease and Gerontopsychiatry/Neurology (P.W.), Bonn University Hospital, Germany.
MDPatrick Oeckl
From the Nuffield Department of Clinical Neurosciences (E.F., E.G., M.R.T.), University of Oxford, UK; Department of Neurology (P.O., P.S., F.V., J.H.W., P.W., A.C.L., M.O.), Ulm University Hospital, Germany; Department of Pathophysiology and Transplantation (F.V., V.S.), Università degli Studi di Milano; Department of Neurology–Stroke Unit and Laboratory of Neuroscience (F.V., C.M., V.S.), IRCCS Istituto Auxologico Italiano, Milan, Italy; Neurologic Clinic and Policlinic, Departments of Medicine, Clinical Research, and Biomedicine (C.B., J.K.), University Hospital and University of Basel, Switzerland; Department of Neurology (P.V.D.) and Laboratory of Molecular Neurobiomarker Research and Laboratory Medicine (K.P.), University Hospitals Leuven; KU Leuven–University of Leuven (P.V.D.); Department of Neurosciences (P.V.D.), VIB–Center for Brain & Disease Research, Leuven, Belgium; Department of Neurology (J.G., P.M., B.S.), Jena University Hospital, Germany; Department of Metabolic Biochemistry (C.J., F.L.) and Neurological Diseases Department (M.d.M.A., F.S.), Hôpitaux Universitaires Pitié Salpêtrière–Charles Foix, Paris, France; Department of Neurology (S.K., S.P.), Hannover Medical School; Institute for Epidemiology and Medical Biometry (B.M.) Ulm University, Germany; Donders Institute for Brain, Cognition and Behaviour, Department of Neurology (J.R., M.M.V.), and Radboud Alzheimer Center, Department of Laboratory Medicine (M.M.V.), Radboud University Medical Center, Nijmegen, the Netherlands; and Department of Neurodegenerative Disease and Gerontopsychiatry/Neurology (P.W.), Bonn University Hospital, Germany.
PhDPetra Steinacker
From the Nuffield Department of Clinical Neurosciences (E.F., E.G., M.R.T.), University of Oxford, UK; Department of Neurology (P.O., P.S., F.V., J.H.W., P.W., A.C.L., M.O.), Ulm University Hospital, Germany; Department of Pathophysiology and Transplantation (F.V., V.S.), Università degli Studi di Milano; Department of Neurology–Stroke Unit and Laboratory of Neuroscience (F.V., C.M., V.S.), IRCCS Istituto Auxologico Italiano, Milan, Italy; Neurologic Clinic and Policlinic, Departments of Medicine, Clinical Research, and Biomedicine (C.B., J.K.), University Hospital and University of Basel, Switzerland; Department of Neurology (P.V.D.) and Laboratory of Molecular Neurobiomarker Research and Laboratory Medicine (K.P.), University Hospitals Leuven; KU Leuven–University of Leuven (P.V.D.); Department of Neurosciences (P.V.D.), VIB–Center for Brain & Disease Research, Leuven, Belgium; Department of Neurology (J.G., P.M., B.S.), Jena University Hospital, Germany; Department of Metabolic Biochemistry (C.J., F.L.) and Neurological Diseases Department (M.d.M.A., F.S.), Hôpitaux Universitaires Pitié Salpêtrière–Charles Foix, Paris, France; Department of Neurology (S.K., S.P.), Hannover Medical School; Institute for Epidemiology and Medical Biometry (B.M.) Ulm University, Germany; Donders Institute for Brain, Cognition and Behaviour, Department of Neurology (J.R., M.M.V.), and Radboud Alzheimer Center, Department of Laboratory Medicine (M.M.V.), Radboud University Medical Center, Nijmegen, the Netherlands; and Department of Neurodegenerative Disease and Gerontopsychiatry/Neurology (P.W.), Bonn University Hospital, Germany.
PhDFederico Verde
From the Nuffield Department of Clinical Neurosciences (E.F., E.G., M.R.T.), University of Oxford, UK; Department of Neurology (P.O., P.S., F.V., J.H.W., P.W., A.C.L., M.O.), Ulm University Hospital, Germany; Department of Pathophysiology and Transplantation (F.V., V.S.), Università degli Studi di Milano; Department of Neurology–Stroke Unit and Laboratory of Neuroscience (F.V., C.M., V.S.), IRCCS Istituto Auxologico Italiano, Milan, Italy; Neurologic Clinic and Policlinic, Departments of Medicine, Clinical Research, and Biomedicine (C.B., J.K.), University Hospital and University of Basel, Switzerland; Department of Neurology (P.V.D.) and Laboratory of Molecular Neurobiomarker Research and Laboratory Medicine (K.P.), University Hospitals Leuven; KU Leuven–University of Leuven (P.V.D.); Department of Neurosciences (P.V.D.), VIB–Center for Brain & Disease Research, Leuven, Belgium; Department of Neurology (J.G., P.M., B.S.), Jena University Hospital, Germany; Department of Metabolic Biochemistry (C.J., F.L.) and Neurological Diseases Department (M.d.M.A., F.S.), Hôpitaux Universitaires Pitié Salpêtrière–Charles Foix, Paris, France; Department of Neurology (S.K., S.P.), Hannover Medical School; Institute for Epidemiology and Medical Biometry (B.M.) Ulm University, Germany; Donders Institute for Brain, Cognition and Behaviour, Department of Neurology (J.R., M.M.V.), and Radboud Alzheimer Center, Department of Laboratory Medicine (M.M.V.), Radboud University Medical Center, Nijmegen, the Netherlands; and Department of Neurodegenerative Disease and Gerontopsychiatry/Neurology (P.W.), Bonn University Hospital, Germany.
MDChristian Barro
From the Nuffield Department of Clinical Neurosciences (E.F., E.G., M.R.T.), University of Oxford, UK; Department of Neurology (P.O., P.S., F.V., J.H.W., P.W., A.C.L., M.O.), Ulm University Hospital, Germany; Department of Pathophysiology and Transplantation (F.V., V.S.), Università degli Studi di Milano; Department of Neurology–Stroke Unit and Laboratory of Neuroscience (F.V., C.M., V.S.), IRCCS Istituto Auxologico Italiano, Milan, Italy; Neurologic Clinic and Policlinic, Departments of Medicine, Clinical Research, and Biomedicine (C.B., J.K.), University Hospital and University of Basel, Switzerland; Department of Neurology (P.V.D.) and Laboratory of Molecular Neurobiomarker Research and Laboratory Medicine (K.P.), University Hospitals Leuven; KU Leuven–University of Leuven (P.V.D.); Department of Neurosciences (P.V.D.), VIB–Center for Brain & Disease Research, Leuven, Belgium; Department of Neurology (J.G., P.M., B.S.), Jena University Hospital, Germany; Department of Metabolic Biochemistry (C.J., F.L.) and Neurological Diseases Department (M.d.M.A., F.S.), Hôpitaux Universitaires Pitié Salpêtrière–Charles Foix, Paris, France; Department of Neurology (S.K., S.P.), Hannover Medical School; Institute for Epidemiology and Medical Biometry (B.M.) Ulm University, Germany; Donders Institute for Brain, Cognition and Behaviour, Department of Neurology (J.R., M.M.V.), and Radboud Alzheimer Center, Department of Laboratory Medicine (M.M.V.), Radboud University Medical Center, Nijmegen, the Netherlands; and Department of Neurodegenerative Disease and Gerontopsychiatry/Neurology (P.W.), Bonn University Hospital, Germany.
Philip Van Damme
From the Nuffield Department of Clinical Neurosciences (E.F., E.G., M.R.T.), University of Oxford, UK; Department of Neurology (P.O., P.S., F.V., J.H.W., P.W., A.C.L., M.O.), Ulm University Hospital, Germany; Department of Pathophysiology and Transplantation (F.V., V.S.), Università degli Studi di Milano; Department of Neurology–Stroke Unit and Laboratory of Neuroscience (F.V., C.M., V.S.), IRCCS Istituto Auxologico Italiano, Milan, Italy; Neurologic Clinic and Policlinic, Departments of Medicine, Clinical Research, and Biomedicine (C.B., J.K.), University Hospital and University of Basel, Switzerland; Department of Neurology (P.V.D.) and Laboratory of Molecular Neurobiomarker Research and Laboratory Medicine (K.P.), University Hospitals Leuven; KU Leuven–University of Leuven (P.V.D.); Department of Neurosciences (P.V.D.), VIB–Center for Brain & Disease Research, Leuven, Belgium; Department of Neurology (J.G., P.M., B.S.), Jena University Hospital, Germany; Department of Metabolic Biochemistry (C.J., F.L.) and Neurological Diseases Department (M.d.M.A., F.S.), Hôpitaux Universitaires Pitié Salpêtrière–Charles Foix, Paris, France; Department of Neurology (S.K., S.P.), Hannover Medical School; Institute for Epidemiology and Medical Biometry (B.M.) Ulm University, Germany; Donders Institute for Brain, Cognition and Behaviour, Department of Neurology (J.R., M.M.V.), and Radboud Alzheimer Center, Department of Laboratory Medicine (M.M.V.), Radboud University Medical Center, Nijmegen, the Netherlands; and Department of Neurodegenerative Disease and Gerontopsychiatry/Neurology (P.W.), Bonn University Hospital, Germany.
MD, PhDElizabeth Gray
From the Nuffield Department of Clinical Neurosciences (E.F., E.G., M.R.T.), University of Oxford, UK; Department of Neurology (P.O., P.S., F.V., J.H.W., P.W., A.C.L., M.O.), Ulm University Hospital, Germany; Department of Pathophysiology and Transplantation (F.V., V.S.), Università degli Studi di Milano; Department of Neurology–Stroke Unit and Laboratory of Neuroscience (F.V., C.M., V.S.), IRCCS Istituto Auxologico Italiano, Milan, Italy; Neurologic Clinic and Policlinic, Departments of Medicine, Clinical Research, and Biomedicine (C.B., J.K.), University Hospital and University of Basel, Switzerland; Department of Neurology (P.V.D.) and Laboratory of Molecular Neurobiomarker Research and Laboratory Medicine (K.P.), University Hospitals Leuven; KU Leuven–University of Leuven (P.V.D.); Department of Neurosciences (P.V.D.), VIB–Center for Brain & Disease Research, Leuven, Belgium; Department of Neurology (J.G., P.M., B.S.), Jena University Hospital, Germany; Department of Metabolic Biochemistry (C.J., F.L.) and Neurological Diseases Department (M.d.M.A., F.S.), Hôpitaux Universitaires Pitié Salpêtrière–Charles Foix, Paris, France; Department of Neurology (S.K., S.P.), Hannover Medical School; Institute for Epidemiology and Medical Biometry (B.M.) Ulm University, Germany; Donders Institute for Brain, Cognition and Behaviour, Department of Neurology (J.R., M.M.V.), and Radboud Alzheimer Center, Department of Laboratory Medicine (M.M.V.), Radboud University Medical Center, Nijmegen, the Netherlands; and Department of Neurodegenerative Disease and Gerontopsychiatry/Neurology (P.W.), Bonn University Hospital, Germany.
PhDJulian Grosskreutz
From the Nuffield Department of Clinical Neurosciences (E.F., E.G., M.R.T.), University of Oxford, UK; Department of Neurology (P.O., P.S., F.V., J.H.W., P.W., A.C.L., M.O.), Ulm University Hospital, Germany; Department of Pathophysiology and Transplantation (F.V., V.S.), Università degli Studi di Milano; Department of Neurology–Stroke Unit and Laboratory of Neuroscience (F.V., C.M., V.S.), IRCCS Istituto Auxologico Italiano, Milan, Italy; Neurologic Clinic and Policlinic, Departments of Medicine, Clinical Research, and Biomedicine (C.B., J.K.), University Hospital and University of Basel, Switzerland; Department of Neurology (P.V.D.) and Laboratory of Molecular Neurobiomarker Research and Laboratory Medicine (K.P.), University Hospitals Leuven; KU Leuven–University of Leuven (P.V.D.); Department of Neurosciences (P.V.D.), VIB–Center for Brain & Disease Research, Leuven, Belgium; Department of Neurology (J.G., P.M., B.S.), Jena University Hospital, Germany; Department of Metabolic Biochemistry (C.J., F.L.) and Neurological Diseases Department (M.d.M.A., F.S.), Hôpitaux Universitaires Pitié Salpêtrière–Charles Foix, Paris, France; Department of Neurology (S.K., S.P.), Hannover Medical School; Institute for Epidemiology and Medical Biometry (B.M.) Ulm University, Germany; Donders Institute for Brain, Cognition and Behaviour, Department of Neurology (J.R., M.M.V.), and Radboud Alzheimer Center, Department of Laboratory Medicine (M.M.V.), Radboud University Medical Center, Nijmegen, the Netherlands; and Department of Neurodegenerative Disease and Gerontopsychiatry/Neurology (P.W.), Bonn University Hospital, Germany.
MDClaude Jardel
From the Nuffield Department of Clinical Neurosciences (E.F., E.G., M.R.T.), University of Oxford, UK; Department of Neurology (P.O., P.S., F.V., J.H.W., P.W., A.C.L., M.O.), Ulm University Hospital, Germany; Department of Pathophysiology and Transplantation (F.V., V.S.), Università degli Studi di Milano; Department of Neurology–Stroke Unit and Laboratory of Neuroscience (F.V., C.M., V.S.), IRCCS Istituto Auxologico Italiano, Milan, Italy; Neurologic Clinic and Policlinic, Departments of Medicine, Clinical Research, and Biomedicine (C.B., J.K.), University Hospital and University of Basel, Switzerland; Department of Neurology (P.V.D.) and Laboratory of Molecular Neurobiomarker Research and Laboratory Medicine (K.P.), University Hospitals Leuven; KU Leuven–University of Leuven (P.V.D.); Department of Neurosciences (P.V.D.), VIB–Center for Brain & Disease Research, Leuven, Belgium; Department of Neurology (J.G., P.M., B.S.), Jena University Hospital, Germany; Department of Metabolic Biochemistry (C.J., F.L.) and Neurological Diseases Department (M.d.M.A., F.S.), Hôpitaux Universitaires Pitié Salpêtrière–Charles Foix, Paris, France; Department of Neurology (S.K., S.P.), Hannover Medical School; Institute for Epidemiology and Medical Biometry (B.M.) Ulm University, Germany; Donders Institute for Brain, Cognition and Behaviour, Department of Neurology (J.R., M.M.V.), and Radboud Alzheimer Center, Department of Laboratory Medicine (M.M.V.), Radboud University Medical Center, Nijmegen, the Netherlands; and Department of Neurodegenerative Disease and Gerontopsychiatry/Neurology (P.W.), Bonn University Hospital, Germany.
PharmD, PhDJens Kuhle
From the Nuffield Department of Clinical Neurosciences (E.F., E.G., M.R.T.), University of Oxford, UK; Department of Neurology (P.O., P.S., F.V., J.H.W., P.W., A.C.L., M.O.), Ulm University Hospital, Germany; Department of Pathophysiology and Transplantation (F.V., V.S.), Università degli Studi di Milano; Department of Neurology–Stroke Unit and Laboratory of Neuroscience (F.V., C.M., V.S.), IRCCS Istituto Auxologico Italiano, Milan, Italy; Neurologic Clinic and Policlinic, Departments of Medicine, Clinical Research, and Biomedicine (C.B., J.K.), University Hospital and University of Basel, Switzerland; Department of Neurology (P.V.D.) and Laboratory of Molecular Neurobiomarker Research and Laboratory Medicine (K.P.), University Hospitals Leuven; KU Leuven–University of Leuven (P.V.D.); Department of Neurosciences (P.V.D.), VIB–Center for Brain & Disease Research, Leuven, Belgium; Department of Neurology (J.G., P.M., B.S.), Jena University Hospital, Germany; Department of Metabolic Biochemistry (C.J., F.L.) and Neurological Diseases Department (M.d.M.A., F.S.), Hôpitaux Universitaires Pitié Salpêtrière–Charles Foix, Paris, France; Department of Neurology (S.K., S.P.), Hannover Medical School; Institute for Epidemiology and Medical Biometry (B.M.) Ulm University, Germany; Donders Institute for Brain, Cognition and Behaviour, Department of Neurology (J.R., M.M.V.), and Radboud Alzheimer Center, Department of Laboratory Medicine (M.M.V.), Radboud University Medical Center, Nijmegen, the Netherlands; and Department of Neurodegenerative Disease and Gerontopsychiatry/Neurology (P.W.), Bonn University Hospital, Germany.
MD, PhDSonja Koerner
From the Nuffield Department of Clinical Neurosciences (E.F., E.G., M.R.T.), University of Oxford, UK; Department of Neurology (P.O., P.S., F.V., J.H.W., P.W., A.C.L., M.O.), Ulm University Hospital, Germany; Department of Pathophysiology and Transplantation (F.V., V.S.), Università degli Studi di Milano; Department of Neurology–Stroke Unit and Laboratory of Neuroscience (F.V., C.M., V.S.), IRCCS Istituto Auxologico Italiano, Milan, Italy; Neurologic Clinic and Policlinic, Departments of Medicine, Clinical Research, and Biomedicine (C.B., J.K.), University Hospital and University of Basel, Switzerland; Department of Neurology (P.V.D.) and Laboratory of Molecular Neurobiomarker Research and Laboratory Medicine (K.P.), University Hospitals Leuven; KU Leuven–University of Leuven (P.V.D.); Department of Neurosciences (P.V.D.), VIB–Center for Brain & Disease Research, Leuven, Belgium; Department of Neurology (J.G., P.M., B.S.), Jena University Hospital, Germany; Department of Metabolic Biochemistry (C.J., F.L.) and Neurological Diseases Department (M.d.M.A., F.S.), Hôpitaux Universitaires Pitié Salpêtrière–Charles Foix, Paris, France; Department of Neurology (S.K., S.P.), Hannover Medical School; Institute for Epidemiology and Medical Biometry (B.M.) Ulm University, Germany; Donders Institute for Brain, Cognition and Behaviour, Department of Neurology (J.R., M.M.V.), and Radboud Alzheimer Center, Department of Laboratory Medicine (M.M.V.), Radboud University Medical Center, Nijmegen, the Netherlands; and Department of Neurodegenerative Disease and Gerontopsychiatry/Neurology (P.W.), Bonn University Hospital, Germany.
MDFoudil Lamari
From the Nuffield Department of Clinical Neurosciences (E.F., E.G., M.R.T.), University of Oxford, UK; Department of Neurology (P.O., P.S., F.V., J.H.W., P.W., A.C.L., M.O.), Ulm University Hospital, Germany; Department of Pathophysiology and Transplantation (F.V., V.S.), Università degli Studi di Milano; Department of Neurology–Stroke Unit and Laboratory of Neuroscience (F.V., C.M., V.S.), IRCCS Istituto Auxologico Italiano, Milan, Italy; Neurologic Clinic and Policlinic, Departments of Medicine, Clinical Research, and Biomedicine (C.B., J.K.), University Hospital and University of Basel, Switzerland; Department of Neurology (P.V.D.) and Laboratory of Molecular Neurobiomarker Research and Laboratory Medicine (K.P.), University Hospitals Leuven; KU Leuven–University of Leuven (P.V.D.); Department of Neurosciences (P.V.D.), VIB–Center for Brain & Disease Research, Leuven, Belgium; Department of Neurology (J.G., P.M., B.S.), Jena University Hospital, Germany; Department of Metabolic Biochemistry (C.J., F.L.) and Neurological Diseases Department (M.d.M.A., F.S.), Hôpitaux Universitaires Pitié Salpêtrière–Charles Foix, Paris, France; Department of Neurology (S.K., S.P.), Hannover Medical School; Institute for Epidemiology and Medical Biometry (B.M.) Ulm University, Germany; Donders Institute for Brain, Cognition and Behaviour, Department of Neurology (J.R., M.M.V.), and Radboud Alzheimer Center, Department of Laboratory Medicine (M.M.V.), Radboud University Medical Center, Nijmegen, the Netherlands; and Department of Neurodegenerative Disease and Gerontopsychiatry/Neurology (P.W.), Bonn University Hospital, Germany.
MD, PhDMaria del Mar Amador
From the Nuffield Department of Clinical Neurosciences (E.F., E.G., M.R.T.), University of Oxford, UK; Department of Neurology (P.O., P.S., F.V., J.H.W., P.W., A.C.L., M.O.), Ulm University Hospital, Germany; Department of Pathophysiology and Transplantation (F.V., V.S.), Università degli Studi di Milano; Department of Neurology–Stroke Unit and Laboratory of Neuroscience (F.V., C.M., V.S.), IRCCS Istituto Auxologico Italiano, Milan, Italy; Neurologic Clinic and Policlinic, Departments of Medicine, Clinical Research, and Biomedicine (C.B., J.K.), University Hospital and University of Basel, Switzerland; Department of Neurology (P.V.D.) and Laboratory of Molecular Neurobiomarker Research and Laboratory Medicine (K.P.), University Hospitals Leuven; KU Leuven–University of Leuven (P.V.D.); Department of Neurosciences (P.V.D.), VIB–Center for Brain & Disease Research, Leuven, Belgium; Department of Neurology (J.G., P.M., B.S.), Jena University Hospital, Germany; Department of Metabolic Biochemistry (C.J., F.L.) and Neurological Diseases Department (M.d.M.A., F.S.), Hôpitaux Universitaires Pitié Salpêtrière–Charles Foix, Paris, France; Department of Neurology (S.K., S.P.), Hannover Medical School; Institute for Epidemiology and Medical Biometry (B.M.) Ulm University, Germany; Donders Institute for Brain, Cognition and Behaviour, Department of Neurology (J.R., M.M.V.), and Radboud Alzheimer Center, Department of Laboratory Medicine (M.M.V.), Radboud University Medical Center, Nijmegen, the Netherlands; and Department of Neurodegenerative Disease and Gerontopsychiatry/Neurology (P.W.), Bonn University Hospital, Germany.
MDBenjamin Mayer
From the Nuffield Department of Clinical Neurosciences (E.F., E.G., M.R.T.), University of Oxford, UK; Department of Neurology (P.O., P.S., F.V., J.H.W., P.W., A.C.L., M.O.), Ulm University Hospital, Germany; Department of Pathophysiology and Transplantation (F.V., V.S.), Università degli Studi di Milano; Department of Neurology–Stroke Unit and Laboratory of Neuroscience (F.V., C.M., V.S.), IRCCS Istituto Auxologico Italiano, Milan, Italy; Neurologic Clinic and Policlinic, Departments of Medicine, Clinical Research, and Biomedicine (C.B., J.K.), University Hospital and University of Basel, Switzerland; Department of Neurology (P.V.D.) and Laboratory of Molecular Neurobiomarker Research and Laboratory Medicine (K.P.), University Hospitals Leuven; KU Leuven–University of Leuven (P.V.D.); Department of Neurosciences (P.V.D.), VIB–Center for Brain & Disease Research, Leuven, Belgium; Department of Neurology (J.G., P.M., B.S.), Jena University Hospital, Germany; Department of Metabolic Biochemistry (C.J., F.L.) and Neurological Diseases Department (M.d.M.A., F.S.), Hôpitaux Universitaires Pitié Salpêtrière–Charles Foix, Paris, France; Department of Neurology (S.K., S.P.), Hannover Medical School; Institute for Epidemiology and Medical Biometry (B.M.) Ulm University, Germany; Donders Institute for Brain, Cognition and Behaviour, Department of Neurology (J.R., M.M.V.), and Radboud Alzheimer Center, Department of Laboratory Medicine (M.M.V.), Radboud University Medical Center, Nijmegen, the Netherlands; and Department of Neurodegenerative Disease and Gerontopsychiatry/Neurology (P.W.), Bonn University Hospital, Germany.
PhDClaudia Morelli
From the Nuffield Department of Clinical Neurosciences (E.F., E.G., M.R.T.), University of Oxford, UK; Department of Neurology (P.O., P.S., F.V., J.H.W., P.W., A.C.L., M.O.), Ulm University Hospital, Germany; Department of Pathophysiology and Transplantation (F.V., V.S.), Università degli Studi di Milano; Department of Neurology–Stroke Unit and Laboratory of Neuroscience (F.V., C.M., V.S.), IRCCS Istituto Auxologico Italiano, Milan, Italy; Neurologic Clinic and Policlinic, Departments of Medicine, Clinical Research, and Biomedicine (C.B., J.K.), University Hospital and University of Basel, Switzerland; Department of Neurology (P.V.D.) and Laboratory of Molecular Neurobiomarker Research and Laboratory Medicine (K.P.), University Hospitals Leuven; KU Leuven–University of Leuven (P.V.D.); Department of Neurosciences (P.V.D.), VIB–Center for Brain & Disease Research, Leuven, Belgium; Department of Neurology (J.G., P.M., B.S.), Jena University Hospital, Germany; Department of Metabolic Biochemistry (C.J., F.L.) and Neurological Diseases Department (M.d.M.A., F.S.), Hôpitaux Universitaires Pitié Salpêtrière–Charles Foix, Paris, France; Department of Neurology (S.K., S.P.), Hannover Medical School; Institute for Epidemiology and Medical Biometry (B.M.) Ulm University, Germany; Donders Institute for Brain, Cognition and Behaviour, Department of Neurology (J.R., M.M.V.), and Radboud Alzheimer Center, Department of Laboratory Medicine (M.M.V.), Radboud University Medical Center, Nijmegen, the Netherlands; and Department of Neurodegenerative Disease and Gerontopsychiatry/Neurology (P.W.), Bonn University Hospital, Germany.
MDPetra Muckova
From the Nuffield Department of Clinical Neurosciences (E.F., E.G., M.R.T.), University of Oxford, UK; Department of Neurology (P.O., P.S., F.V., J.H.W., P.W., A.C.L., M.O.), Ulm University Hospital, Germany; Department of Pathophysiology and Transplantation (F.V., V.S.), Università degli Studi di Milano; Department of Neurology–Stroke Unit and Laboratory of Neuroscience (F.V., C.M., V.S.), IRCCS Istituto Auxologico Italiano, Milan, Italy; Neurologic Clinic and Policlinic, Departments of Medicine, Clinical Research, and Biomedicine (C.B., J.K.), University Hospital and University of Basel, Switzerland; Department of Neurology (P.V.D.) and Laboratory of Molecular Neurobiomarker Research and Laboratory Medicine (K.P.), University Hospitals Leuven; KU Leuven–University of Leuven (P.V.D.); Department of Neurosciences (P.V.D.), VIB–Center for Brain & Disease Research, Leuven, Belgium; Department of Neurology (J.G., P.M., B.S.), Jena University Hospital, Germany; Department of Metabolic Biochemistry (C.J., F.L.) and Neurological Diseases Department (M.d.M.A., F.S.), Hôpitaux Universitaires Pitié Salpêtrière–Charles Foix, Paris, France; Department of Neurology (S.K., S.P.), Hannover Medical School; Institute for Epidemiology and Medical Biometry (B.M.) Ulm University, Germany; Donders Institute for Brain, Cognition and Behaviour, Department of Neurology (J.R., M.M.V.), and Radboud Alzheimer Center, Department of Laboratory Medicine (M.M.V.), Radboud University Medical Center, Nijmegen, the Netherlands; and Department of Neurodegenerative Disease and Gerontopsychiatry/Neurology (P.W.), Bonn University Hospital, Germany.
PhDSusanne Petri
From the Nuffield Department of Clinical Neurosciences (E.F., E.G., M.R.T.), University of Oxford, UK; Department of Neurology (P.O., P.S., F.V., J.H.W., P.W., A.C.L., M.O.), Ulm University Hospital, Germany; Department of Pathophysiology and Transplantation (F.V., V.S.), Università degli Studi di Milano; Department of Neurology–Stroke Unit and Laboratory of Neuroscience (F.V., C.M., V.S.), IRCCS Istituto Auxologico Italiano, Milan, Italy; Neurologic Clinic and Policlinic, Departments of Medicine, Clinical Research, and Biomedicine (C.B., J.K.), University Hospital and University of Basel, Switzerland; Department of Neurology (P.V.D.) and Laboratory of Molecular Neurobiomarker Research and Laboratory Medicine (K.P.), University Hospitals Leuven; KU Leuven–University of Leuven (P.V.D.); Department of Neurosciences (P.V.D.), VIB–Center for Brain & Disease Research, Leuven, Belgium; Department of Neurology (J.G., P.M., B.S.), Jena University Hospital, Germany; Department of Metabolic Biochemistry (C.J., F.L.) and Neurological Diseases Department (M.d.M.A., F.S.), Hôpitaux Universitaires Pitié Salpêtrière–Charles Foix, Paris, France; Department of Neurology (S.K., S.P.), Hannover Medical School; Institute for Epidemiology and Medical Biometry (B.M.) Ulm University, Germany; Donders Institute for Brain, Cognition and Behaviour, Department of Neurology (J.R., M.M.V.), and Radboud Alzheimer Center, Department of Laboratory Medicine (M.M.V.), Radboud University Medical Center, Nijmegen, the Netherlands; and Department of Neurodegenerative Disease and Gerontopsychiatry/Neurology (P.W.), Bonn University Hospital, Germany.
MDKoen Poesen
From the Nuffield Department of Clinical Neurosciences (E.F., E.G., M.R.T.), University of Oxford, UK; Department of Neurology (P.O., P.S., F.V., J.H.W., P.W., A.C.L., M.O.), Ulm University Hospital, Germany; Department of Pathophysiology and Transplantation (F.V., V.S.), Università degli Studi di Milano; Department of Neurology–Stroke Unit and Laboratory of Neuroscience (F.V., C.M., V.S.), IRCCS Istituto Auxologico Italiano, Milan, Italy; Neurologic Clinic and Policlinic, Departments of Medicine, Clinical Research, and Biomedicine (C.B., J.K.), University Hospital and University of Basel, Switzerland; Department of Neurology (P.V.D.) and Laboratory of Molecular Neurobiomarker Research and Laboratory Medicine (K.P.), University Hospitals Leuven; KU Leuven–University of Leuven (P.V.D.); Department of Neurosciences (P.V.D.), VIB–Center for Brain & Disease Research, Leuven, Belgium; Department of Neurology (J.G., P.M., B.S.), Jena University Hospital, Germany; Department of Metabolic Biochemistry (C.J., F.L.) and Neurological Diseases Department (M.d.M.A., F.S.), Hôpitaux Universitaires Pitié Salpêtrière–Charles Foix, Paris, France; Department of Neurology (S.K., S.P.), Hannover Medical School; Institute for Epidemiology and Medical Biometry (B.M.) Ulm University, Germany; Donders Institute for Brain, Cognition and Behaviour, Department of Neurology (J.R., M.M.V.), and Radboud Alzheimer Center, Department of Laboratory Medicine (M.M.V.), Radboud University Medical Center, Nijmegen, the Netherlands; and Department of Neurodegenerative Disease and Gerontopsychiatry/Neurology (P.W.), Bonn University Hospital, Germany.
PharmD, PhDJoost Raaphorst
From the Nuffield Department of Clinical Neurosciences (E.F., E.G., M.R.T.), University of Oxford, UK; Department of Neurology (P.O., P.S., F.V., J.H.W., P.W., A.C.L., M.O.), Ulm University Hospital, Germany; Department of Pathophysiology and Transplantation (F.V., V.S.), Università degli Studi di Milano; Department of Neurology–Stroke Unit and Laboratory of Neuroscience (F.V., C.M., V.S.), IRCCS Istituto Auxologico Italiano, Milan, Italy; Neurologic Clinic and Policlinic, Departments of Medicine, Clinical Research, and Biomedicine (C.B., J.K.), University Hospital and University of Basel, Switzerland; Department of Neurology (P.V.D.) and Laboratory of Molecular Neurobiomarker Research and Laboratory Medicine (K.P.), University Hospitals Leuven; KU Leuven–University of Leuven (P.V.D.); Department of Neurosciences (P.V.D.), VIB–Center for Brain & Disease Research, Leuven, Belgium; Department of Neurology (J.G., P.M., B.S.), Jena University Hospital, Germany; Department of Metabolic Biochemistry (C.J., F.L.) and Neurological Diseases Department (M.d.M.A., F.S.), Hôpitaux Universitaires Pitié Salpêtrière–Charles Foix, Paris, France; Department of Neurology (S.K., S.P.), Hannover Medical School; Institute for Epidemiology and Medical Biometry (B.M.) Ulm University, Germany; Donders Institute for Brain, Cognition and Behaviour, Department of Neurology (J.R., M.M.V.), and Radboud Alzheimer Center, Department of Laboratory Medicine (M.M.V.), Radboud University Medical Center, Nijmegen, the Netherlands; and Department of Neurodegenerative Disease and Gerontopsychiatry/Neurology (P.W.), Bonn University Hospital, Germany.
MDFrançois Salachas
From the Nuffield Department of Clinical Neurosciences (E.F., E.G., M.R.T.), University of Oxford, UK; Department of Neurology (P.O., P.S., F.V., J.H.W., P.W., A.C.L., M.O.), Ulm University Hospital, Germany; Department of Pathophysiology and Transplantation (F.V., V.S.), Università degli Studi di Milano; Department of Neurology–Stroke Unit and Laboratory of Neuroscience (F.V., C.M., V.S.), IRCCS Istituto Auxologico Italiano, Milan, Italy; Neurologic Clinic and Policlinic, Departments of Medicine, Clinical Research, and Biomedicine (C.B., J.K.), University Hospital and University of Basel, Switzerland; Department of Neurology (P.V.D.) and Laboratory of Molecular Neurobiomarker Research and Laboratory Medicine (K.P.), University Hospitals Leuven; KU Leuven–University of Leuven (P.V.D.); Department of Neurosciences (P.V.D.), VIB–Center for Brain & Disease Research, Leuven, Belgium; Department of Neurology (J.G., P.M., B.S.), Jena University Hospital, Germany; Department of Metabolic Biochemistry (C.J., F.L.) and Neurological Diseases Department (M.d.M.A., F.S.), Hôpitaux Universitaires Pitié Salpêtrière–Charles Foix, Paris, France; Department of Neurology (S.K., S.P.), Hannover Medical School; Institute for Epidemiology and Medical Biometry (B.M.) Ulm University, Germany; Donders Institute for Brain, Cognition and Behaviour, Department of Neurology (J.R., M.M.V.), and Radboud Alzheimer Center, Department of Laboratory Medicine (M.M.V.), Radboud University Medical Center, Nijmegen, the Netherlands; and Department of Neurodegenerative Disease and Gerontopsychiatry/Neurology (P.W.), Bonn University Hospital, Germany.
MDVincenzo Silani
From the Nuffield Department of Clinical Neurosciences (E.F., E.G., M.R.T.), University of Oxford, UK; Department of Neurology (P.O., P.S., F.V., J.H.W., P.W., A.C.L., M.O.), Ulm University Hospital, Germany; Department of Pathophysiology and Transplantation (F.V., V.S.), Università degli Studi di Milano; Department of Neurology–Stroke Unit and Laboratory of Neuroscience (F.V., C.M., V.S.), IRCCS Istituto Auxologico Italiano, Milan, Italy; Neurologic Clinic and Policlinic, Departments of Medicine, Clinical Research, and Biomedicine (C.B., J.K.), University Hospital and University of Basel, Switzerland; Department of Neurology (P.V.D.) and Laboratory of Molecular Neurobiomarker Research and Laboratory Medicine (K.P.), University Hospitals Leuven; KU Leuven–University of Leuven (P.V.D.); Department of Neurosciences (P.V.D.), VIB–Center for Brain & Disease Research, Leuven, Belgium; Department of Neurology (J.G., P.M., B.S.), Jena University Hospital, Germany; Department of Metabolic Biochemistry (C.J., F.L.) and Neurological Diseases Department (M.d.M.A., F.S.), Hôpitaux Universitaires Pitié Salpêtrière–Charles Foix, Paris, France; Department of Neurology (S.K., S.P.), Hannover Medical School; Institute for Epidemiology and Medical Biometry (B.M.) Ulm University, Germany; Donders Institute for Brain, Cognition and Behaviour, Department of Neurology (J.R., M.M.V.), and Radboud Alzheimer Center, Department of Laboratory Medicine (M.M.V.), Radboud University Medical Center, Nijmegen, the Netherlands; and Department of Neurodegenerative Disease and Gerontopsychiatry/Neurology (P.W.), Bonn University Hospital, Germany.
MDBeatrice Stubendorff
From the Nuffield Department of Clinical Neurosciences (E.F., E.G., M.R.T.), University of Oxford, UK; Department of Neurology (P.O., P.S., F.V., J.H.W., P.W., A.C.L., M.O.), Ulm University Hospital, Germany; Department of Pathophysiology and Transplantation (F.V., V.S.), Università degli Studi di Milano; Department of Neurology–Stroke Unit and Laboratory of Neuroscience (F.V., C.M., V.S.), IRCCS Istituto Auxologico Italiano, Milan, Italy; Neurologic Clinic and Policlinic, Departments of Medicine, Clinical Research, and Biomedicine (C.B., J.K.), University Hospital and University of Basel, Switzerland; Department of Neurology (P.V.D.) and Laboratory of Molecular Neurobiomarker Research and Laboratory Medicine (K.P.), University Hospitals Leuven; KU Leuven–University of Leuven (P.V.D.); Department of Neurosciences (P.V.D.), VIB–Center for Brain & Disease Research, Leuven, Belgium; Department of Neurology (J.G., P.M., B.S.), Jena University Hospital, Germany; Department of Metabolic Biochemistry (C.J., F.L.) and Neurological Diseases Department (M.d.M.A., F.S.), Hôpitaux Universitaires Pitié Salpêtrière–Charles Foix, Paris, France; Department of Neurology (S.K., S.P.), Hannover Medical School; Institute for Epidemiology and Medical Biometry (B.M.) Ulm University, Germany; Donders Institute for Brain, Cognition and Behaviour, Department of Neurology (J.R., M.M.V.), and Radboud Alzheimer Center, Department of Laboratory Medicine (M.M.V.), Radboud University Medical Center, Nijmegen, the Netherlands; and Department of Neurodegenerative Disease and Gerontopsychiatry/Neurology (P.W.), Bonn University Hospital, Germany.
PhDMartin R. Turner
From the Nuffield Department of Clinical Neurosciences (E.F., E.G., M.R.T.), University of Oxford, UK; Department of Neurology (P.O., P.S., F.V., J.H.W., P.W., A.C.L., M.O.), Ulm University Hospital, Germany; Department of Pathophysiology and Transplantation (F.V., V.S.), Università degli Studi di Milano; Department of Neurology–Stroke Unit and Laboratory of Neuroscience (F.V., C.M., V.S.), IRCCS Istituto Auxologico Italiano, Milan, Italy; Neurologic Clinic and Policlinic, Departments of Medicine, Clinical Research, and Biomedicine (C.B., J.K.), University Hospital and University of Basel, Switzerland; Department of Neurology (P.V.D.) and Laboratory of Molecular Neurobiomarker Research and Laboratory Medicine (K.P.), University Hospitals Leuven; KU Leuven–University of Leuven (P.V.D.); Department of Neurosciences (P.V.D.), VIB–Center for Brain & Disease Research, Leuven, Belgium; Department of Neurology (J.G., P.M., B.S.), Jena University Hospital, Germany; Department of Metabolic Biochemistry (C.J., F.L.) and Neurological Diseases Department (M.d.M.A., F.S.), Hôpitaux Universitaires Pitié Salpêtrière–Charles Foix, Paris, France; Department of Neurology (S.K., S.P.), Hannover Medical School; Institute for Epidemiology and Medical Biometry (B.M.) Ulm University, Germany; Donders Institute for Brain, Cognition and Behaviour, Department of Neurology (J.R., M.M.V.), and Radboud Alzheimer Center, Department of Laboratory Medicine (M.M.V.), Radboud University Medical Center, Nijmegen, the Netherlands; and Department of Neurodegenerative Disease and Gerontopsychiatry/Neurology (P.W.), Bonn University Hospital, Germany.
PhDMarcel M. Verbeek
From the Nuffield Department of Clinical Neurosciences (E.F., E.G., M.R.T.), University of Oxford, UK; Department of Neurology (P.O., P.S., F.V., J.H.W., P.W., A.C.L., M.O.), Ulm University Hospital, Germany; Department of Pathophysiology and Transplantation (F.V., V.S.), Università degli Studi di Milano; Department of Neurology–Stroke Unit and Laboratory of Neuroscience (F.V., C.M., V.S.), IRCCS Istituto Auxologico Italiano, Milan, Italy; Neurologic Clinic and Policlinic, Departments of Medicine, Clinical Research, and Biomedicine (C.B., J.K.), University Hospital and University of Basel, Switzerland; Department of Neurology (P.V.D.) and Laboratory of Molecular Neurobiomarker Research and Laboratory Medicine (K.P.), University Hospitals Leuven; KU Leuven–University of Leuven (P.V.D.); Department of Neurosciences (P.V.D.), VIB–Center for Brain & Disease Research, Leuven, Belgium; Department of Neurology (J.G., P.M., B.S.), Jena University Hospital, Germany; Department of Metabolic Biochemistry (C.J., F.L.) and Neurological Diseases Department (M.d.M.A., F.S.), Hôpitaux Universitaires Pitié Salpêtrière–Charles Foix, Paris, France; Department of Neurology (S.K., S.P.), Hannover Medical School; Institute for Epidemiology and Medical Biometry (B.M.) Ulm University, Germany; Donders Institute for Brain, Cognition and Behaviour, Department of Neurology (J.R., M.M.V.), and Radboud Alzheimer Center, Department of Laboratory Medicine (M.M.V.), Radboud University Medical Center, Nijmegen, the Netherlands; and Department of Neurodegenerative Disease and Gerontopsychiatry/Neurology (P.W.), Bonn University Hospital, Germany.
PhD, MScJochen H. Weishaupt
From the Nuffield Department of Clinical Neurosciences (E.F., E.G., M.R.T.), University of Oxford, UK; Department of Neurology (P.O., P.S., F.V., J.H.W., P.W., A.C.L., M.O.), Ulm University Hospital, Germany; Department of Pathophysiology and Transplantation (F.V., V.S.), Università degli Studi di Milano; Department of Neurology–Stroke Unit and Laboratory of Neuroscience (F.V., C.M., V.S.), IRCCS Istituto Auxologico Italiano, Milan, Italy; Neurologic Clinic and Policlinic, Departments of Medicine, Clinical Research, and Biomedicine (C.B., J.K.), University Hospital and University of Basel, Switzerland; Department of Neurology (P.V.D.) and Laboratory of Molecular Neurobiomarker Research and Laboratory Medicine (K.P.), University Hospitals Leuven; KU Leuven–University of Leuven (P.V.D.); Department of Neurosciences (P.V.D.), VIB–Center for Brain & Disease Research, Leuven, Belgium; Department of Neurology (J.G., P.M., B.S.), Jena University Hospital, Germany; Department of Metabolic Biochemistry (C.J., F.L.) and Neurological Diseases Department (M.d.M.A., F.S.), Hôpitaux Universitaires Pitié Salpêtrière–Charles Foix, Paris, France; Department of Neurology (S.K., S.P.), Hannover Medical School; Institute for Epidemiology and Medical Biometry (B.M.) Ulm University, Germany; Donders Institute for Brain, Cognition and Behaviour, Department of Neurology (J.R., M.M.V.), and Radboud Alzheimer Center, Department of Laboratory Medicine (M.M.V.), Radboud University Medical Center, Nijmegen, the Netherlands; and Department of Neurodegenerative Disease and Gerontopsychiatry/Neurology (P.W.), Bonn University Hospital, Germany.
MDPatrick Weydt
From the Nuffield Department of Clinical Neurosciences (E.F., E.G., M.R.T.), University of Oxford, UK; Department of Neurology (P.O., P.S., F.V., J.H.W., P.W., A.C.L., M.O.), Ulm University Hospital, Germany; Department of Pathophysiology and Transplantation (F.V., V.S.), Università degli Studi di Milano; Department of Neurology–Stroke Unit and Laboratory of Neuroscience (F.V., C.M., V.S.), IRCCS Istituto Auxologico Italiano, Milan, Italy; Neurologic Clinic and Policlinic, Departments of Medicine, Clinical Research, and Biomedicine (C.B., J.K.), University Hospital and University of Basel, Switzerland; Department of Neurology (P.V.D.) and Laboratory of Molecular Neurobiomarker Research and Laboratory Medicine (K.P.), University Hospitals Leuven; KU Leuven–University of Leuven (P.V.D.); Department of Neurosciences (P.V.D.), VIB–Center for Brain & Disease Research, Leuven, Belgium; Department of Neurology (J.G., P.M., B.S.), Jena University Hospital, Germany; Department of Metabolic Biochemistry (C.J., F.L.) and Neurological Diseases Department (M.d.M.A., F.S.), Hôpitaux Universitaires Pitié Salpêtrière–Charles Foix, Paris, France; Department of Neurology (S.K., S.P.), Hannover Medical School; Institute for Epidemiology and Medical Biometry (B.M.) Ulm University, Germany; Donders Institute for Brain, Cognition and Behaviour, Department of Neurology (J.R., M.M.V.), and Radboud Alzheimer Center, Department of Laboratory Medicine (M.M.V.), Radboud University Medical Center, Nijmegen, the Netherlands; and Department of Neurodegenerative Disease and Gerontopsychiatry/Neurology (P.W.), Bonn University Hospital, Germany.
MDAlbert C. Ludolph
From the Nuffield Department of Clinical Neurosciences (E.F., E.G., M.R.T.), University of Oxford, UK; Department of Neurology (P.O., P.S., F.V., J.H.W., P.W., A.C.L., M.O.), Ulm University Hospital, Germany; Department of Pathophysiology and Transplantation (F.V., V.S.), Università degli Studi di Milano; Department of Neurology–Stroke Unit and Laboratory of Neuroscience (F.V., C.M., V.S.), IRCCS Istituto Auxologico Italiano, Milan, Italy; Neurologic Clinic and Policlinic, Departments of Medicine, Clinical Research, and Biomedicine (C.B., J.K.), University Hospital and University of Basel, Switzerland; Department of Neurology (P.V.D.) and Laboratory of Molecular Neurobiomarker Research and Laboratory Medicine (K.P.), University Hospitals Leuven; KU Leuven–University of Leuven (P.V.D.); Department of Neurosciences (P.V.D.), VIB–Center for Brain & Disease Research, Leuven, Belgium; Department of Neurology (J.G., P.M., B.S.), Jena University Hospital, Germany; Department of Metabolic Biochemistry (C.J., F.L.) and Neurological Diseases Department (M.d.M.A., F.S.), Hôpitaux Universitaires Pitié Salpêtrière–Charles Foix, Paris, France; Department of Neurology (S.K., S.P.), Hannover Medical School; Institute for Epidemiology and Medical Biometry (B.M.) Ulm University, Germany; Donders Institute for Brain, Cognition and Behaviour, Department of Neurology (J.R., M.M.V.), and Radboud Alzheimer Center, Department of Laboratory Medicine (M.M.V.), Radboud University Medical Center, Nijmegen, the Netherlands; and Department of Neurodegenerative Disease and Gerontopsychiatry/Neurology (P.W.), Bonn University Hospital, Germany.
MDMarkus Otto
From the Nuffield Department of Clinical Neurosciences (E.F., E.G., M.R.T.), University of Oxford, UK; Department of Neurology (P.O., P.S., F.V., J.H.W., P.W., A.C.L., M.O.), Ulm University Hospital, Germany; Department of Pathophysiology and Transplantation (F.V., V.S.), Università degli Studi di Milano; Department of Neurology–Stroke Unit and Laboratory of Neuroscience (F.V., C.M., V.S.), IRCCS Istituto Auxologico Italiano, Milan, Italy; Neurologic Clinic and Policlinic, Departments of Medicine, Clinical Research, and Biomedicine (C.B., J.K.), University Hospital and University of Basel, Switzerland; Department of Neurology (P.V.D.) and Laboratory of Molecular Neurobiomarker Research and Laboratory Medicine (K.P.), University Hospitals Leuven; KU Leuven–University of Leuven (P.V.D.); Department of Neurosciences (P.V.D.), VIB–Center for Brain & Disease Research, Leuven, Belgium; Department of Neurology (J.G., P.M., B.S.), Jena University Hospital, Germany; Department of Metabolic Biochemistry (C.J., F.L.) and Neurological Diseases Department (M.d.M.A., F.S.), Hôpitaux Universitaires Pitié Salpêtrière–Charles Foix, Paris, France; Department of Neurology (S.K., S.P.), Hannover Medical School; Institute for Epidemiology and Medical Biometry (B.M.) Ulm University, Germany; Donders Institute for Brain, Cognition and Behaviour, Department of Neurology (J.R., M.M.V.), and Radboud Alzheimer Center, Department of Laboratory Medicine (M.M.V.), Radboud University Medical Center, Nijmegen, the Netherlands; and Department of Neurodegenerative Disease and Gerontopsychiatry/Neurology (P.W.), Bonn University Hospital, Germany.
MDMulticenter evaluation of neurofilaments in early symptom onset amyotrophic lateral sclerosis
Emily Feneberg, Patrick Oeckl, Petra Steinacker, Federico Verde, Christian Barro, Philip Van Damme, Elizabeth Gray, Julian Grosskreutz, Claude Jardel, Jens Kuhle, Sonja Koerner, Foudil Lamari, Maria del Mar Amador, Benjamin Mayer, Claudia Morelli, Petra Muckova, Susanne Petri, Koen Poesen, Joost Raaphorst, François Salachas, Vincenzo Silani, Beatrice Stubendorff, Martin R. Turner, Marcel M. Verbeek, Jochen H. Weishaupt, Patrick Weydt, Albert C. Ludolph, Markus Otto
Neurology Jan 2018, 90 (1) e22-e30; DOI: 10.1212/WNL.0000000000004761
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Abstract
Objective To examine neurofilament (Nf) concentrations according to symptom onset and clinical diagnostic certainty categories of amyotrophic lateral sclerosis (ALS).
Methods We measured Nf light chain (NfL) and phosphorylated Nf heavy chain (pNfH) CSF and NfL serum levels in patients with ALS with first symptom onset ≤6 months (n = 54) or >6 months (n = 135) from sampling, and patients with other neurologic diseases, differential diagnoses of a motor neuron disease (MND mimics), and other MND variants to determine the diagnostic accuracy in patients with ALS with early symptom onset. Samples were received multicentric and analyzed by ELISA and Simoa platform and related to other clinical measures.
Results NfL and pNfH in CSF and NfL in serum were increased in early and later symptomatic phase ALS (p < 0.0001). CSF and serum NfL and CSF pNfH discriminated patients with ALS with early symptom onset from those with other neurologic diseases and MND mimics with high sensitivity (94%, 88%, 98%, and 89%, 100%, 78%) and specificity (86%, 92%, 91%, and 94%, 90%, 98%) and did not vary between clinical diagnostic categories of ALS in the early symptomatic phase group. Baseline NfL and pNfH levels were not significantly different in patients with ALS with clinical progression to definite or probable ALS at follow-up.
Conclusion The measurement of Nf has potential to enhance diagnostic accuracy of ALS in those presenting soon after symptom onset, and is measurable across multiple centers.
Classification of evidence This study provides Class II evidence that CSF and serum Nf concentrations discriminate ALS with early symptom onset from other neurologic diseases.
Glossary
- ALS=
- amyotrophic lateral sclerosis;
- ALSFRS-R=
- Revised ALS Functional Rating Scale;
- AUC=
- area under the curve;
- CI=
- confidence interval;
- LMN=
- lower motor neuron;
- mAb=
- monoclonal antibodies;
- MND=
- motor neuron disease;
- Nf=
- neurofilament;
- NfL=
- neurofilament light chain;
- pNfH=
- phosphorylated neurofilament heavy chain;
- UMN=
- upper motor neuron
Footnotes
Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
- Received February 15, 2017.
- Accepted in final form September 21, 2017.
- Copyright © 2017 American Academy of Neurology
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