title: CSF neurofilament light differs in neurodegenerative diseases and predicts severity and survival.
abstract: OBJECTIVE
  We hypothesized that CSF neurofilament light (NFL) levels would be elevated in dementias with subcortical involvement, including vascular dementia (VaD), but less elevated in dementias primarily affecting gray matter structures, such as Alzheimer disease (AD), and that elevated CSF NFL would correlate with disease severity and shorter survival time irrespective of clinical diagnosis.
  
  
  METHODS
  We included 3,356 individuals with dementia who had CSF NFL analyzed in our laboratory between 2005 and 2012. Clinical diagnoses and Mini-Mental State Examination (MMSE) scores were obtained from the Swedish Dementia Registry, and in selected cases (n = 478), date of death from the Swedish Mortality Registry.
  
  
  RESULTS
  CSF NFL differed among clinical diagnoses, with the highest levels seen in frontotemporal dementia, VaD, and mixed AD and VaD. Early-onset AD (younger than 65 years) had the lowest levels. High CSF NFL correlated with low MMSE score and short survival time irrespective of diagnosis, and was also particularly evident in AD.
  
  
  CONCLUSIONS
  CSF NFL differs among different neurodegenerative diseases and is especially high in dementias engaging subcortical brain regions, such as VaD and mixed AD and VaD, but also in frontotemporal dementia. The association of high CSF NFL levels with disease severity and short survival supports the notion that high CSF NFL levels indicate more aggressive disease processes.
authors.affiliation: From the Clinical Neurochemistry Laboratory (T.S., C.R., N.M., K.B., H.Z.), Institute of Neuroscience and Physiology, Department of Neurochemistry, the Sahlgrenska Academy at the University of Gothenburg, Mölndal; Division of Clinical Geriatrics, Department of Neurobiology, Care Sciences, and Society (B.F., D.R., B.W., M.E.), and KI Alzheimer Disease Research Center (A.W.), Karolinska Institutet, Stockholm; Department of Geriatric Medicine (B.F., D.R., M.E.), Karolinska University Hospital, Stockholm, Sweden; Centre for Statistical Methodology (J.W.B.), London School of Hygiene & Tropical Medicine, London, UK; Department of Veterans Affairs Medical Center (N.M.), Center for Imaging of Neurodegenerative Diseases, San Francisco, CA; Clinical Memory Research Unit (K.N.), Department of Clinical Sciences Malmö, Lund University, Malmö; Department of Public Health and Caring Sciences/Geriatrics (L.K.), Uppsala University; Institute of Neuroscience and Physiology (L.R.), Department of Neurology, the Sahlgrenska Academy at the University of Gothenburg, Sweden; and UCL Institute of Neurology (J.M.S., H.Z.), Queen Square, London, UK. tobias.skillback@neuro.gu.se.
authors.forename: Tobias
authors.initials: T
authors.lastname: Skillbäck
authors.affiliation: From the Clinical Neurochemistry Laboratory (T.S., C.R., N.M., K.B., H.Z.), Institute of Neuroscience and Physiology, Department of Neurochemistry, the Sahlgrenska Academy at the University of Gothenburg, Mölndal; Division of Clinical Geriatrics, Department of Neurobiology, Care Sciences, and Society (B.F., D.R., B.W., M.E.), and KI Alzheimer Disease Research Center (A.W.), Karolinska Institutet, Stockholm; Department of Geriatric Medicine (B.F., D.R., M.E.), Karolinska University Hospital, Stockholm, Sweden; Centre for Statistical Methodology (J.W.B.), London School of Hygiene & Tropical Medicine, London, UK; Department of Veterans Affairs Medical Center (N.M.), Center for Imaging of Neurodegenerative Diseases, San Francisco, CA; Clinical Memory Research Unit (K.N.), Department of Clinical Sciences Malmö, Lund University, Malmö; Department of Public Health and Caring Sciences/Geriatrics (L.K.), Uppsala University; Institute of Neuroscience and Physiology (L.R.), Department of Neurology, the Sahlgrenska Academy at the University of Gothenburg, Sweden; and UCL Institute of Neurology (J.M.S., H.Z.), Queen Square, London, UK.
authors.forename: Bahman
authors.initials: B
authors.lastname: Farahmand
authors.affiliation: From the Clinical Neurochemistry Laboratory (T.S., C.R., N.M., K.B., H.Z.), Institute of Neuroscience and Physiology, Department of Neurochemistry, the Sahlgrenska Academy at the University of Gothenburg, Mölndal; Division of Clinical Geriatrics, Department of Neurobiology, Care Sciences, and Society (B.F., D.R., B.W., M.E.), and KI Alzheimer Disease Research Center (A.W.), Karolinska Institutet, Stockholm; Department of Geriatric Medicine (B.F., D.R., M.E.), Karolinska University Hospital, Stockholm, Sweden; Centre for Statistical Methodology (J.W.B.), London School of Hygiene & Tropical Medicine, London, UK; Department of Veterans Affairs Medical Center (N.M.), Center for Imaging of Neurodegenerative Diseases, San Francisco, CA; Clinical Memory Research Unit (K.N.), Department of Clinical Sciences Malmö, Lund University, Malmö; Department of Public Health and Caring Sciences/Geriatrics (L.K.), Uppsala University; Institute of Neuroscience and Physiology (L.R.), Department of Neurology, the Sahlgrenska Academy at the University of Gothenburg, Sweden; and UCL Institute of Neurology (J.M.S., H.Z.), Queen Square, London, UK.
authors.forename: Jonathan W
authors.initials: JW
authors.lastname: Bartlett
authors.affiliation: From the Clinical Neurochemistry Laboratory (T.S., C.R., N.M., K.B., H.Z.), Institute of Neuroscience and Physiology, Department of Neurochemistry, the Sahlgrenska Academy at the University of Gothenburg, Mölndal; Division of Clinical Geriatrics, Department of Neurobiology, Care Sciences, and Society (B.F., D.R., B.W., M.E.), and KI Alzheimer Disease Research Center (A.W.), Karolinska Institutet, Stockholm; Department of Geriatric Medicine (B.F., D.R., M.E.), Karolinska University Hospital, Stockholm, Sweden; Centre for Statistical Methodology (J.W.B.), London School of Hygiene & Tropical Medicine, London, UK; Department of Veterans Affairs Medical Center (N.M.), Center for Imaging of Neurodegenerative Diseases, San Francisco, CA; Clinical Memory Research Unit (K.N.), Department of Clinical Sciences Malmö, Lund University, Malmö; Department of Public Health and Caring Sciences/Geriatrics (L.K.), Uppsala University; Institute of Neuroscience and Physiology (L.R.), Department of Neurology, the Sahlgrenska Academy at the University of Gothenburg, Sweden; and UCL Institute of Neurology (J.M.S., H.Z.), Queen Square, London, UK.
authors.forename: Christoffer
authors.initials: C
authors.lastname: Rosén
authors.affiliation: From the Clinical Neurochemistry Laboratory (T.S., C.R., N.M., K.B., H.Z.), Institute of Neuroscience and Physiology, Department of Neurochemistry, the Sahlgrenska Academy at the University of Gothenburg, Mölndal; Division of Clinical Geriatrics, Department of Neurobiology, Care Sciences, and Society (B.F., D.R., B.W., M.E.), and KI Alzheimer Disease Research Center (A.W.), Karolinska Institutet, Stockholm; Department of Geriatric Medicine (B.F., D.R., M.E.), Karolinska University Hospital, Stockholm, Sweden; Centre for Statistical Methodology (J.W.B.), London School of Hygiene & Tropical Medicine, London, UK; Department of Veterans Affairs Medical Center (N.M.), Center for Imaging of Neurodegenerative Diseases, San Francisco, CA; Clinical Memory Research Unit (K.N.), Department of Clinical Sciences Malmö, Lund University, Malmö; Department of Public Health and Caring Sciences/Geriatrics (L.K.), Uppsala University; Institute of Neuroscience and Physiology (L.R.), Department of Neurology, the Sahlgrenska Academy at the University of Gothenburg, Sweden; and UCL Institute of Neurology (J.M.S., H.Z.), Queen Square, London, UK.
authors.forename: Niklas
authors.initials: N
authors.lastname: Mattsson
authors.affiliation: From the Clinical Neurochemistry Laboratory (T.S., C.R., N.M., K.B., H.Z.), Institute of Neuroscience and Physiology, Department of Neurochemistry, the Sahlgrenska Academy at the University of Gothenburg, Mölndal; Division of Clinical Geriatrics, Department of Neurobiology, Care Sciences, and Society (B.F., D.R., B.W., M.E.), and KI Alzheimer Disease Research Center (A.W.), Karolinska Institutet, Stockholm; Department of Geriatric Medicine (B.F., D.R., M.E.), Karolinska University Hospital, Stockholm, Sweden; Centre for Statistical Methodology (J.W.B.), London School of Hygiene & Tropical Medicine, London, UK; Department of Veterans Affairs Medical Center (N.M.), Center for Imaging of Neurodegenerative Diseases, San Francisco, CA; Clinical Memory Research Unit (K.N.), Department of Clinical Sciences Malmö, Lund University, Malmö; Department of Public Health and Caring Sciences/Geriatrics (L.K.), Uppsala University; Institute of Neuroscience and Physiology (L.R.), Department of Neurology, the Sahlgrenska Academy at the University of Gothenburg, Sweden; and UCL Institute of Neurology (J.M.S., H.Z.), Queen Square, London, UK.
authors.forename: Katarina
authors.initials: K
authors.lastname: Nägga
authors.affiliation: From the Clinical Neurochemistry Laboratory (T.S., C.R., N.M., K.B., H.Z.), Institute of Neuroscience and Physiology, Department of Neurochemistry, the Sahlgrenska Academy at the University of Gothenburg, Mölndal; Division of Clinical Geriatrics, Department of Neurobiology, Care Sciences, and Society (B.F., D.R., B.W., M.E.), and KI Alzheimer Disease Research Center (A.W.), Karolinska Institutet, Stockholm; Department of Geriatric Medicine (B.F., D.R., M.E.), Karolinska University Hospital, Stockholm, Sweden; Centre for Statistical Methodology (J.W.B.), London School of Hygiene & Tropical Medicine, London, UK; Department of Veterans Affairs Medical Center (N.M.), Center for Imaging of Neurodegenerative Diseases, San Francisco, CA; Clinical Memory Research Unit (K.N.), Department of Clinical Sciences Malmö, Lund University, Malmö; Department of Public Health and Caring Sciences/Geriatrics (L.K.), Uppsala University; Institute of Neuroscience and Physiology (L.R.), Department of Neurology, the Sahlgrenska Academy at the University of Gothenburg, Sweden; and UCL Institute of Neurology (J.M.S., H.Z.), Queen Square, London, UK.
authors.forename: Lena
authors.initials: L
authors.lastname: Kilander
authors.affiliation: From the Clinical Neurochemistry Laboratory (T.S., C.R., N.M., K.B., H.Z.), Institute of Neuroscience and Physiology, Department of Neurochemistry, the Sahlgrenska Academy at the University of Gothenburg, Mölndal; Division of Clinical Geriatrics, Department of Neurobiology, Care Sciences, and Society (B.F., D.R., B.W., M.E.), and KI Alzheimer Disease Research Center (A.W.), Karolinska Institutet, Stockholm; Department of Geriatric Medicine (B.F., D.R., M.E.), Karolinska University Hospital, Stockholm, Sweden; Centre for Statistical Methodology (J.W.B.), London School of Hygiene & Tropical Medicine, London, UK; Department of Veterans Affairs Medical Center (N.M.), Center for Imaging of Neurodegenerative Diseases, San Francisco, CA; Clinical Memory Research Unit (K.N.), Department of Clinical Sciences Malmö, Lund University, Malmö; Department of Public Health and Caring Sciences/Geriatrics (L.K.), Uppsala University; Institute of Neuroscience and Physiology (L.R.), Department of Neurology, the Sahlgrenska Academy at the University of Gothenburg, Sweden; and UCL Institute of Neurology (J.M.S., H.Z.), Queen Square, London, UK.
authors.forename: Dorota
authors.initials: D
authors.lastname: Religa
authors.affiliation: From the Clinical Neurochemistry Laboratory (T.S., C.R., N.M., K.B., H.Z.), Institute of Neuroscience and Physiology, Department of Neurochemistry, the Sahlgrenska Academy at the University of Gothenburg, Mölndal; Division of Clinical Geriatrics, Department of Neurobiology, Care Sciences, and Society (B.F., D.R., B.W., M.E.), and KI Alzheimer Disease Research Center (A.W.), Karolinska Institutet, Stockholm; Department of Geriatric Medicine (B.F., D.R., M.E.), Karolinska University Hospital, Stockholm, Sweden; Centre for Statistical Methodology (J.W.B.), London School of Hygiene & Tropical Medicine, London, UK; Department of Veterans Affairs Medical Center (N.M.), Center for Imaging of Neurodegenerative Diseases, San Francisco, CA; Clinical Memory Research Unit (K.N.), Department of Clinical Sciences Malmö, Lund University, Malmö; Department of Public Health and Caring Sciences/Geriatrics (L.K.), Uppsala University; Institute of Neuroscience and Physiology (L.R.), Department of Neurology, the Sahlgrenska Academy at the University of Gothenburg, Sweden; and UCL Institute of Neurology (J.M.S., H.Z.), Queen Square, London, UK.
authors.forename: Anders
authors.initials: A
authors.lastname: Wimo
authors.affiliation: From the Clinical Neurochemistry Laboratory (T.S., C.R., N.M., K.B., H.Z.), Institute of Neuroscience and Physiology, Department of Neurochemistry, the Sahlgrenska Academy at the University of Gothenburg, Mölndal; Division of Clinical Geriatrics, Department of Neurobiology, Care Sciences, and Society (B.F., D.R., B.W., M.E.), and KI Alzheimer Disease Research Center (A.W.), Karolinska Institutet, Stockholm; Department of Geriatric Medicine (B.F., D.R., M.E.), Karolinska University Hospital, Stockholm, Sweden; Centre for Statistical Methodology (J.W.B.), London School of Hygiene & Tropical Medicine, London, UK; Department of Veterans Affairs Medical Center (N.M.), Center for Imaging of Neurodegenerative Diseases, San Francisco, CA; Clinical Memory Research Unit (K.N.), Department of Clinical Sciences Malmö, Lund University, Malmö; Department of Public Health and Caring Sciences/Geriatrics (L.K.), Uppsala University; Institute of Neuroscience and Physiology (L.R.), Department of Neurology, the Sahlgrenska Academy at the University of Gothenburg, Sweden; and UCL Institute of Neurology (J.M.S., H.Z.), Queen Square, London, UK.
authors.forename: Bengt
authors.initials: B
authors.lastname: Winblad
authors.affiliation: From the Clinical Neurochemistry Laboratory (T.S., C.R., N.M., K.B., H.Z.), Institute of Neuroscience and Physiology, Department of Neurochemistry, the Sahlgrenska Academy at the University of Gothenburg, Mölndal; Division of Clinical Geriatrics, Department of Neurobiology, Care Sciences, and Society (B.F., D.R., B.W., M.E.), and KI Alzheimer Disease Research Center (A.W.), Karolinska Institutet, Stockholm; Department of Geriatric Medicine (B.F., D.R., M.E.), Karolinska University Hospital, Stockholm, Sweden; Centre for Statistical Methodology (J.W.B.), London School of Hygiene & Tropical Medicine, London, UK; Department of Veterans Affairs Medical Center (N.M.), Center for Imaging of Neurodegenerative Diseases, San Francisco, CA; Clinical Memory Research Unit (K.N.), Department of Clinical Sciences Malmö, Lund University, Malmö; Department of Public Health and Caring Sciences/Geriatrics (L.K.), Uppsala University; Institute of Neuroscience and Physiology (L.R.), Department of Neurology, the Sahlgrenska Academy at the University of Gothenburg, Sweden; and UCL Institute of Neurology (J.M.S., H.Z.), Queen Square, London, UK.
authors.forename: Lars
authors.initials: L
authors.lastname: Rosengren
authors.affiliation: From the Clinical Neurochemistry Laboratory (T.S., C.R., N.M., K.B., H.Z.), Institute of Neuroscience and Physiology, Department of Neurochemistry, the Sahlgrenska Academy at the University of Gothenburg, Mölndal; Division of Clinical Geriatrics, Department of Neurobiology, Care Sciences, and Society (B.F., D.R., B.W., M.E.), and KI Alzheimer Disease Research Center (A.W.), Karolinska Institutet, Stockholm; Department of Geriatric Medicine (B.F., D.R., M.E.), Karolinska University Hospital, Stockholm, Sweden; Centre for Statistical Methodology (J.W.B.), London School of Hygiene & Tropical Medicine, London, UK; Department of Veterans Affairs Medical Center (N.M.), Center for Imaging of Neurodegenerative Diseases, San Francisco, CA; Clinical Memory Research Unit (K.N.), Department of Clinical Sciences Malmö, Lund University, Malmö; Department of Public Health and Caring Sciences/Geriatrics (L.K.), Uppsala University; Institute of Neuroscience and Physiology (L.R.), Department of Neurology, the Sahlgrenska Academy at the University of Gothenburg, Sweden; and UCL Institute of Neurology (J.M.S., H.Z.), Queen Square, London, UK.
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Schott
authors.affiliation: From the Clinical Neurochemistry Laboratory (T.S., C.R., N.M., K.B., H.Z.), Institute of Neuroscience and Physiology, Department of Neurochemistry, the Sahlgrenska Academy at the University of Gothenburg, Mölndal; Division of Clinical Geriatrics, Department of Neurobiology, Care Sciences, and Society (B.F., D.R., B.W., M.E.), and KI Alzheimer Disease Research Center (A.W.), Karolinska Institutet, Stockholm; Department of Geriatric Medicine (B.F., D.R., M.E.), Karolinska University Hospital, Stockholm, Sweden; Centre for Statistical Methodology (J.W.B.), London School of Hygiene & Tropical Medicine, London, UK; Department of Veterans Affairs Medical Center (N.M.), Center for Imaging of Neurodegenerative Diseases, San Francisco, CA; Clinical Memory Research Unit (K.N.), Department of Clinical Sciences Malmö, Lund University, Malmö; Department of Public Health and Caring Sciences/Geriatrics (L.K.), Uppsala University; Institute of Neuroscience and Physiology (L.R.), Department of Neurology, the Sahlgrenska Academy at the University of Gothenburg, Sweden; and UCL Institute of Neurology (J.M.S., H.Z.), Queen Square, London, UK.
authors.forename: Kaj
authors.initials: K
authors.lastname: Blennow
authors.affiliation: From the Clinical Neurochemistry Laboratory (T.S., C.R., N.M., K.B., H.Z.), Institute of Neuroscience and Physiology, Department of Neurochemistry, the Sahlgrenska Academy at the University of Gothenburg, Mölndal; Division of Clinical Geriatrics, Department of Neurobiology, Care Sciences, and Society (B.F., D.R., B.W., M.E.), and KI Alzheimer Disease Research Center (A.W.), Karolinska Institutet, Stockholm; Department of Geriatric Medicine (B.F., D.R., M.E.), Karolinska University Hospital, Stockholm, Sweden; Centre for Statistical Methodology (J.W.B.), London School of Hygiene & Tropical Medicine, London, UK; Department of Veterans Affairs Medical Center (N.M.), Center for Imaging of Neurodegenerative Diseases, San Francisco, CA; Clinical Memory Research Unit (K.N.), Department of Clinical Sciences Malmö, Lund University, Malmö; Department of Public Health and Caring Sciences/Geriatrics (L.K.), Uppsala University; Institute of Neuroscience and Physiology (L.R.), Department of Neurology, the Sahlgrenska Academy at the University of Gothenburg, Sweden; and UCL Institute of Neurology (J.M.S., H.Z.), Queen Square, London, UK.
authors.forename: Maria
authors.initials: M
authors.lastname: Eriksdotter
authors.affiliation: From the Clinical Neurochemistry Laboratory (T.S., C.R., N.M., K.B., H.Z.), Institute of Neuroscience and Physiology, Department of Neurochemistry, the Sahlgrenska Academy at the University of Gothenburg, Mölndal; Division of Clinical Geriatrics, Department of Neurobiology, Care Sciences, and Society (B.F., D.R., B.W., M.E.), and KI Alzheimer Disease Research Center (A.W.), Karolinska Institutet, Stockholm; Department of Geriatric Medicine (B.F., D.R., M.E.), Karolinska University Hospital, Stockholm, Sweden; Centre for Statistical Methodology (J.W.B.), London School of Hygiene & Tropical Medicine, London, UK; Department of Veterans Affairs Medical Center (N.M.), Center for Imaging of Neurodegenerative Diseases, San Francisco, CA; Clinical Memory Research Unit (K.N.), Department of Clinical Sciences Malmö, Lund University, Malmö; Department of Public Health and Caring Sciences/Geriatrics (L.K.), Uppsala University; Institute of Neuroscience and Physiology (L.R.), Department of Neurology, the Sahlgrenska Academy at the University of Gothenburg, Sweden; and UCL Institute of Neurology (J.M.S., H.Z.), Queen Square, London, UK.
authors.forename: Henrik
authors.initials: H
authors.lastname: Zetterberg
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000134:cerebrospinal fluid; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D019636:Neurodegenerative Diseases / Q000134:cerebrospinal fluid* / Q000175:diagnosis / Q000401:mortality*; D016900:Neurofilament Proteins / Q000134:cerebrospinal fluid*; D011237:Predictive Value of Tests; D012042:Registries; D012720:Severity of Illness Index; D015996:Survival Rate / Q000639:trends
chemical_list: D015415:Biomarkers; D016900:Neurofilament Proteins; C044882:neurofilament protein L