title: Serum neurofilament light chain protein is a measure of disease intensity in frontotemporal dementia.
abstract: OBJECTIVE
  To investigate serum neurofilament light chain (NfL) concentrations in frontotemporal dementia (FTD) and to see whether they are associated with the severity of disease.
  
  
  METHODS
  Serum samples were collected from 74 participants (34 with behavioral variant FTD [bvFTD], 3 with FTD and motor neuron disease and 37 with primary progressive aphasia [PPA]) and 28 healthy controls. Twenty-four of the FTD participants carried a pathogenic mutation in C9orf72 (9), microtubule-associated protein tau (MAPT; 11), or progranulin (GRN; 4). Serum NfL concentrations were determined with the NF-Light kit transferred onto the single-molecule array platform and compared between FTD and healthy controls and between the FTD clinical and genetic subtypes. We also assessed the relationship between NfL concentrations and measures of cognition and brain volume.
  
  
  RESULTS
  Serum NfL concentrations were higher in patients with FTD overall (mean 77.9 pg/mL [SD 51.3 pg/mL]) than controls (19.6 pg/mL [SD 8.2 pg/mL]; p < 0.001). Concentrations were also significantly higher in bvFTD (57.8 pg/mL [SD 33.1 pg/mL]) and both the semantic and nonfluent variants of PPA (95.9 and 82.5 pg/mL [SD 33.0 and 33.8 pg/mL], respectively) compared with controls and in semantic variant PPA compared with logopenic variant PPA. Concentrations were significantly higher than controls in both the C9orf72 and MAPT subgroups (79.2 and 40.5 pg/mL [SD 48.2 and 20.9 pg/mL], respectively) with a trend to a higher level in the GRN subgroup (138.5 pg/mL [SD 103.3 pg/mL). However, there was variability within all groups. Serum concentrations correlated particularly with frontal lobe atrophy rate (r = 0.53, p = 0.003).
  
  
  CONCLUSIONS
  Increased serum NfL concentrations are seen in FTD but show wide variability within each clinical and genetic group. Higher concentrations may reflect the intensity of the disease in FTD and are associated with more rapid atrophy of the frontal lobes.
authors: From the Dementia Research Centre (J.D.R., I.O.C.W., K.M.D., E.B., E.G., A.F., M.J.C., S.O., J.M.N., J.M.S., N.C.F., J.D.W.), MRC Prion Unit (S.M., R.D.), Department of Neurodegenerative Disease, and Department of Molecular Neuroscience (J.T., H.Z.), UCL Institute of Neurology, Queen Square; Centre for Medical Image Computing (J.M.C., S.O.), University College London; Department of Medical Statistics (J.M.N.), London School of Hygiene and Tropical Medicine, UK; UmanDiagnostics (N.N.), Umeå; and Clinical Neurochemistry Laboratory (U.A., K.B., H.Z.), Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden. j.rohrer@ucl.ac.uk.
authors: Jonathan D
authors: JD
authors: Rohrer
authors: From the Dementia Research Centre (J.D.R., I.O.C.W., K.M.D., E.B., E.G., A.F., M.J.C., S.O., J.M.N., J.M.S., N.C.F., J.D.W.), MRC Prion Unit (S.M., R.D.), Department of Neurodegenerative Disease, and Department of Molecular Neuroscience (J.T., H.Z.), UCL Institute of Neurology, Queen Square; Centre for Medical Image Computing (J.M.C., S.O.), University College London; Department of Medical Statistics (J.M.N.), London School of Hygiene and Tropical Medicine, UK; UmanDiagnostics (N.N.), Umeå; and Clinical Neurochemistry Laboratory (U.A., K.B., H.Z.), Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
authors: Ione O C
authors: IO
authors: Woollacott
authors: From the Dementia Research Centre (J.D.R., I.O.C.W., K.M.D., E.B., E.G., A.F., M.J.C., S.O., J.M.N., J.M.S., N.C.F., J.D.W.), MRC Prion Unit (S.M., R.D.), Department of Neurodegenerative Disease, and Department of Molecular Neuroscience (J.T., H.Z.), UCL Institute of Neurology, Queen Square; Centre for Medical Image Computing (J.M.C., S.O.), University College London; Department of Medical Statistics (J.M.N.), London School of Hygiene and Tropical Medicine, UK; UmanDiagnostics (N.N.), Umeå; and Clinical Neurochemistry Laboratory (U.A., K.B., H.Z.), Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
authors: Katrina M
authors: KM
authors: Dick
authors: From the Dementia Research Centre (J.D.R., I.O.C.W., K.M.D., E.B., E.G., A.F., M.J.C., S.O., J.M.N., J.M.S., N.C.F., J.D.W.), MRC Prion Unit (S.M., R.D.), Department of Neurodegenerative Disease, and Department of Molecular Neuroscience (J.T., H.Z.), UCL Institute of Neurology, Queen Square; Centre for Medical Image Computing (J.M.C., S.O.), University College London; Department of Medical Statistics (J.M.N.), London School of Hygiene and Tropical Medicine, UK; UmanDiagnostics (N.N.), Umeå; and Clinical Neurochemistry Laboratory (U.A., K.B., H.Z.), Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
authors: Emilie
authors: E
authors: Brotherhood
authors: From the Dementia Research Centre (J.D.R., I.O.C.W., K.M.D., E.B., E.G., A.F., M.J.C., S.O., J.M.N., J.M.S., N.C.F., J.D.W.), MRC Prion Unit (S.M., R.D.), Department of Neurodegenerative Disease, and Department of Molecular Neuroscience (J.T., H.Z.), UCL Institute of Neurology, Queen Square; Centre for Medical Image Computing (J.M.C., S.O.), University College London; Department of Medical Statistics (J.M.N.), London School of Hygiene and Tropical Medicine, UK; UmanDiagnostics (N.N.), Umeå; and Clinical Neurochemistry Laboratory (U.A., K.B., H.Z.), Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
authors: Elizabeth
authors: E
authors: Gordon
authors: From the Dementia Research Centre (J.D.R., I.O.C.W., K.M.D., E.B., E.G., A.F., M.J.C., S.O., J.M.N., J.M.S., N.C.F., J.D.W.), MRC Prion Unit (S.M., R.D.), Department of Neurodegenerative Disease, and Department of Molecular Neuroscience (J.T., H.Z.), UCL Institute of Neurology, Queen Square; Centre for Medical Image Computing (J.M.C., S.O.), University College London; Department of Medical Statistics (J.M.N.), London School of Hygiene and Tropical Medicine, UK; UmanDiagnostics (N.N.), Umeå; and Clinical Neurochemistry Laboratory (U.A., K.B., H.Z.), Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
authors: Alexander
authors: A
authors: Fellows
authors: From the Dementia Research Centre (J.D.R., I.O.C.W., K.M.D., E.B., E.G., A.F., M.J.C., S.O., J.M.N., J.M.S., N.C.F., J.D.W.), MRC Prion Unit (S.M., R.D.), Department of Neurodegenerative Disease, and Department of Molecular Neuroscience (J.T., H.Z.), UCL Institute of Neurology, Queen Square; Centre for Medical Image Computing (J.M.C., S.O.), University College London; Department of Medical Statistics (J.M.N.), London School of Hygiene and Tropical Medicine, UK; UmanDiagnostics (N.N.), Umeå; and Clinical Neurochemistry Laboratory (U.A., K.B., H.Z.), Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
authors: Jamie
authors: J
authors: Toombs
authors: From the Dementia Research Centre (J.D.R., I.O.C.W., K.M.D., E.B., E.G., A.F., M.J.C., S.O., J.M.N., J.M.S., N.C.F., J.D.W.), MRC Prion Unit (S.M., R.D.), Department of Neurodegenerative Disease, and Department of Molecular Neuroscience (J.T., H.Z.), UCL Institute of Neurology, Queen Square; Centre for Medical Image Computing (J.M.C., S.O.), University College London; Department of Medical Statistics (J.M.N.), London School of Hygiene and Tropical Medicine, UK; UmanDiagnostics (N.N.), Umeå; and Clinical Neurochemistry Laboratory (U.A., K.B., H.Z.), Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
authors: Ronald
authors: R
authors: Druyeh
authors: From the Dementia Research Centre (J.D.R., I.O.C.W., K.M.D., E.B., E.G., A.F., M.J.C., S.O., J.M.N., J.M.S., N.C.F., J.D.W.), MRC Prion Unit (S.M., R.D.), Department of Neurodegenerative Disease, and Department of Molecular Neuroscience (J.T., H.Z.), UCL Institute of Neurology, Queen Square; Centre for Medical Image Computing (J.M.C., S.O.), University College London; Department of Medical Statistics (J.M.N.), London School of Hygiene and Tropical Medicine, UK; UmanDiagnostics (N.N.), Umeå; and Clinical Neurochemistry Laboratory (U.A., K.B., H.Z.), Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
authors: M Jorge
authors: MJ
authors: Cardoso
authors: From the Dementia Research Centre (J.D.R., I.O.C.W., K.M.D., E.B., E.G., A.F., M.J.C., S.O., J.M.N., J.M.S., N.C.F., J.D.W.), MRC Prion Unit (S.M., R.D.), Department of Neurodegenerative Disease, and Department of Molecular Neuroscience (J.T., H.Z.), UCL Institute of Neurology, Queen Square; Centre for Medical Image Computing (J.M.C., S.O.), University College London; Department of Medical Statistics (J.M.N.), London School of Hygiene and Tropical Medicine, UK; UmanDiagnostics (N.N.), Umeå; and Clinical Neurochemistry Laboratory (U.A., K.B., H.Z.), Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
authors: Sebastien
authors: S
authors: Ourselin
authors: From the Dementia Research Centre (J.D.R., I.O.C.W., K.M.D., E.B., E.G., A.F., M.J.C., S.O., J.M.N., J.M.S., N.C.F., J.D.W.), MRC Prion Unit (S.M., R.D.), Department of Neurodegenerative Disease, and Department of Molecular Neuroscience (J.T., H.Z.), UCL Institute of Neurology, Queen Square; Centre for Medical Image Computing (J.M.C., S.O.), University College London; Department of Medical Statistics (J.M.N.), London School of Hygiene and Tropical Medicine, UK; UmanDiagnostics (N.N.), Umeå; and Clinical Neurochemistry Laboratory (U.A., K.B., H.Z.), Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
authors: Jennifer M
authors: JM
authors: Nicholas
authors: From the Dementia Research Centre (J.D.R., I.O.C.W., K.M.D., E.B., E.G., A.F., M.J.C., S.O., J.M.N., J.M.S., N.C.F., J.D.W.), MRC Prion Unit (S.M., R.D.), Department of Neurodegenerative Disease, and Department of Molecular Neuroscience (J.T., H.Z.), UCL Institute of Neurology, Queen Square; Centre for Medical Image Computing (J.M.C., S.O.), University College London; Department of Medical Statistics (J.M.N.), London School of Hygiene and Tropical Medicine, UK; UmanDiagnostics (N.N.), Umeå; and Clinical Neurochemistry Laboratory (U.A., K.B., H.Z.), Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
authors: Niklas
authors: N
authors: Norgren
authors: From the Dementia Research Centre (J.D.R., I.O.C.W., K.M.D., E.B., E.G., A.F., M.J.C., S.O., J.M.N., J.M.S., N.C.F., J.D.W.), MRC Prion Unit (S.M., R.D.), Department of Neurodegenerative Disease, and Department of Molecular Neuroscience (J.T., H.Z.), UCL Institute of Neurology, Queen Square; Centre for Medical Image Computing (J.M.C., S.O.), University College London; Department of Medical Statistics (J.M.N.), London School of Hygiene and Tropical Medicine, UK; UmanDiagnostics (N.N.), Umeå; and Clinical Neurochemistry Laboratory (U.A., K.B., H.Z.), Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
authors: Simon
authors: S
authors: Mead
authors: From the Dementia Research Centre (J.D.R., I.O.C.W., K.M.D., E.B., E.G., A.F., M.J.C., S.O., J.M.N., J.M.S., N.C.F., J.D.W.), MRC Prion Unit (S.M., R.D.), Department of Neurodegenerative Disease, and Department of Molecular Neuroscience (J.T., H.Z.), UCL Institute of Neurology, Queen Square; Centre for Medical Image Computing (J.M.C., S.O.), University College London; Department of Medical Statistics (J.M.N.), London School of Hygiene and Tropical Medicine, UK; UmanDiagnostics (N.N.), Umeå; and Clinical Neurochemistry Laboratory (U.A., K.B., H.Z.), Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
authors: Ulf
authors: U
authors: Andreasson
authors: From the Dementia Research Centre (J.D.R., I.O.C.W., K.M.D., E.B., E.G., A.F., M.J.C., S.O., J.M.N., J.M.S., N.C.F., J.D.W.), MRC Prion Unit (S.M., R.D.), Department of Neurodegenerative Disease, and Department of Molecular Neuroscience (J.T., H.Z.), UCL Institute of Neurology, Queen Square; Centre for Medical Image Computing (J.M.C., S.O.), University College London; Department of Medical Statistics (J.M.N.), London School of Hygiene and Tropical Medicine, UK; UmanDiagnostics (N.N.), Umeå; and Clinical Neurochemistry Laboratory (U.A., K.B., H.Z.), Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
authors: Kaj
authors: K
authors: Blennow
authors: From the Dementia Research Centre (J.D.R., I.O.C.W., K.M.D., E.B., E.G., A.F., M.J.C., S.O., J.M.N., J.M.S., N.C.F., J.D.W.), MRC Prion Unit (S.M., R.D.), Department of Neurodegenerative Disease, and Department of Molecular Neuroscience (J.T., H.Z.), UCL Institute of Neurology, Queen Square; Centre for Medical Image Computing (J.M.C., S.O.), University College London; Department of Medical Statistics (J.M.N.), London School of Hygiene and Tropical Medicine, UK; UmanDiagnostics (N.N.), Umeå; and Clinical Neurochemistry Laboratory (U.A., K.B., H.Z.), Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
authors: Jonathan M
authors: JM
authors: Schott
authors: From the Dementia Research Centre (J.D.R., I.O.C.W., K.M.D., E.B., E.G., A.F., M.J.C., S.O., J.M.N., J.M.S., N.C.F., J.D.W.), MRC Prion Unit (S.M., R.D.), Department of Neurodegenerative Disease, and Department of Molecular Neuroscience (J.T., H.Z.), UCL Institute of Neurology, Queen Square; Centre for Medical Image Computing (J.M.C., S.O.), University College London; Department of Medical Statistics (J.M.N.), London School of Hygiene and Tropical Medicine, UK; UmanDiagnostics (N.N.), Umeå; and Clinical Neurochemistry Laboratory (U.A., K.B., H.Z.), Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
authors: Nick C
authors: NC
authors: Fox
authors: From the Dementia Research Centre (J.D.R., I.O.C.W., K.M.D., E.B., E.G., A.F., M.J.C., S.O., J.M.N., J.M.S., N.C.F., J.D.W.), MRC Prion Unit (S.M., R.D.), Department of Neurodegenerative Disease, and Department of Molecular Neuroscience (J.T., H.Z.), UCL Institute of Neurology, Queen Square; Centre for Medical Image Computing (J.M.C., S.O.), University College London; Department of Medical Statistics (J.M.N.), London School of Hygiene and Tropical Medicine, UK; UmanDiagnostics (N.N.), Umeå; and Clinical Neurochemistry Laboratory (U.A., K.B., H.Z.), Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
authors: Jason D
authors: JD
authors: Warren
authors: From the Dementia Research Centre (J.D.R., I.O.C.W., K.M.D., E.B., E.G., A.F., M.J.C., S.O., J.M.N., J.M.S., N.C.F., J.D.W.), MRC Prion Unit (S.M., R.D.), Department of Neurodegenerative Disease, and Department of Molecular Neuroscience (J.T., H.Z.), UCL Institute of Neurology, Queen Square; Centre for Medical Image Computing (J.M.C., S.O.), University College London; Department of Medical Statistics (J.M.N.), London School of Hygiene and Tropical Medicine, UK; UmanDiagnostics (N.N.), Umeå; and Clinical Neurochemistry Laboratory (U.A., K.B., H.Z.), Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
authors: Henrik
authors: H
authors: Zetterberg
mesh_terms: D000368:Aged; D018888:Aphasia, Primary Progressive / Q000097:blood / Q000000981:diagnostic imaging / Q000235:genetics; D001284:Atrophy; D015415:Biomarkers / Q000097:blood; D000073885:C9orf72 Protein; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D005625:Frontal Lobe / Q000000981:diagnostic imaging; D057180:Frontotemporal Dementia / Q000097:blood* / Q000000981:diagnostic imaging / Q000235:genetics; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D016472:Motor Neuron Disease / Q000097:blood / Q000000981:diagnostic imaging / Q000235:genetics; D016900:Neurofilament Proteins / Q000097:blood*; D000077153:Progranulins; D011506:Proteins / Q000235:genetics; D011594:Psychometrics; D012720:Severity of Illness Index; D016875:tau Proteins / Q000235:genetics
chemical_list: D015415:Biomarkers; D000073885:C9orf72 Protein; C568651:C9orf72 protein, human; C492314:GRN protein, human; D036341:Intercellular Signaling Peptides and Proteins; C054369:MAPT protein, human; D016900:Neurofilament Proteins; D000077153:Progranulins; D011506:Proteins; C044882:neurofilament protein L; D016875:tau Proteins