Multicenter evaluation of neurofilaments in early symptom onset amyotrophic lateral sclerosis.
Journal article

Multicenter evaluation of neurofilaments in early symptom onset amyotrophic lateral sclerosis.

  • Feneberg E 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.
  • Oeckl P 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.
  • Steinacker P 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.
  • Verde F 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.
  • Barro C 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.
  • Van Damme P 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.
  • Gray E 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.
  • Grosskreutz J 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.
  • Jardel C 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.
  • Kuhle J 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.
  • Koerner S 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.
  • Lamari F 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.
  • Amador MDM 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.
  • Mayer B 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.
  • Morelli C 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.
  • Muckova P 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.
  • Petri S 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.
  • Poesen K 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.
  • Raaphorst J 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.
  • Salachas F 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.
  • Silani V 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.
  • Stubendorff B 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.
  • Turner MR 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.
  • Verbeek MM 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.
  • Weishaupt JH 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.
  • Weydt P 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.
  • Ludolph AC 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.
  • Otto M 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. markus.otto@uni-ulm.de.
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  • 2017-12-08
Published in:
  • Neurology. - 2018
English 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.
Language
  • English
Open access status
closed
Identifiers
Persistent URL
https://folia.unifr.ch/global/documents/49949
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