Serum neurofilament light chain in behavioral variant frontotemporal dementia

Petra Steinacker; Sarah Anderl-Straub; Janine Diehl-Schmid; Elisa Semler; Ingo Uttner; Christine A F von Arnim; Henryk Barthel; Adrian Danek; Klaus Fassbender; Klaus Fliessbach; Hans Foerstl; Timo Grimmer; Hans-Jürgen Huppertz; Holger Jahn; Jan Kassubek; Johannes Kornhuber; Bernhard Landwehrmeyer; Martin Lauer; Juan Manuel Maler; Benjamin Mayer; Patrick Oeckl; Johannes Prudlo; Anja Schneider; Alexander E Volk; Jens Wiltfang; Matthias L Schroeter; Albert C Ludolph; Markus Otto; FTLDc study group

doi:10.1212/WNL.0000000000006318

Serum neurofilament light chain in behavioral variant frontotemporal dementia

Neurology. 2018 Oct 9;91(15):e1390-e1401. doi: 10.1212/WNL.0000000000006318. Epub 2018 Sep 12.

Authors

Petra Steinacker¹, Sarah Anderl-Straub¹, Janine Diehl-Schmid¹, Elisa Semler¹, Ingo Uttner¹, Christine A F von Arnim¹, Henryk Barthel¹, Adrian Danek¹, Klaus Fassbender¹, Klaus Fliessbach¹, Hans Foerstl¹, Timo Grimmer¹, Hans-Jürgen Huppertz¹, Holger Jahn¹, Jan Kassubek¹, Johannes Kornhuber¹, Bernhard Landwehrmeyer¹, Martin Lauer¹, Juan Manuel Maler¹, Benjamin Mayer¹, Patrick Oeckl¹, Johannes Prudlo¹, Anja Schneider¹, Alexander E Volk¹, Jens Wiltfang¹, Matthias L Schroeter¹, Albert C Ludolph¹, Markus Otto²; FTLDc study group

Affiliations

¹ From the Department of Neurology (P.S., S.A.-S., E.S., I.U., C.A.F.v.A., J. Kassubek, B.L., P.O., A.C.L., M.O.) and Institute of Epidemiology and Medical Biometry (B.M.), University of Ulm; Department of Psychiatry and Psychotherapy (J.D.-S., H.F., T.G.), Klinikum Rechts der Isar, Technical University of Munich; Department of Nuclear Medicine (H.B.), Leipzig University Hospital; Department of Neurology (A.D.), Ludwig-Maximilians-University, Munich; Department of Neurology (K.F.), Saarland University, Homburg; Department of Psychiatry and Psychotherapy (K.F.), University of Bonn, Germany; Swiss Epilepsy Center (H.-J.H.), Zurich, Switzerland; Department of Psychiatry and Psychotherapy (H.J.), University Medical Center Hamburg-Eppendorf, Hamburg; AMEOS Klinikum (H.J.), Heiligenhafen; Department of Psychiatry and Psychotherapy (J. Kornhuber, J.M.M.), Friedrich-Alexander-University of Erlangen-Nuremberg, Erlangen; Department of Psychiatry and Psychotherapy (M.L.), University of Würzburg; Department of Neurology (J.P.), University of Rostock; DZNE (J.P.), Rostock; Department of Neurodegenerative Diseases and Geriatric Psychiatry (A.S.), University Hospital Bonn; DZNE (A.S.), Bonn; Institute of Human Genetics (A.E.V.), University Medical Center Hamburg-Eppendorf, Hamburg; Department of Psychiatry and Psychotherapy (J.W.), University Medical Center Göttingen; DZNE (J.W.), Göttingen, Germany; iBiMED (J.W.), Medical Sciences Department, University of Aveiro, Portugal; Clinic for Cognitive Neurology (M.L.S.), University Clinic Leipzig; and Max Planck Institute for Human Cognitive and Brain Sciences (M.L.S.), Leipzig, Germany.
² From the Department of Neurology (P.S., S.A.-S., E.S., I.U., C.A.F.v.A., J. Kassubek, B.L., P.O., A.C.L., M.O.) and Institute of Epidemiology and Medical Biometry (B.M.), University of Ulm; Department of Psychiatry and Psychotherapy (J.D.-S., H.F., T.G.), Klinikum Rechts der Isar, Technical University of Munich; Department of Nuclear Medicine (H.B.), Leipzig University Hospital; Department of Neurology (A.D.), Ludwig-Maximilians-University, Munich; Department of Neurology (K.F.), Saarland University, Homburg; Department of Psychiatry and Psychotherapy (K.F.), University of Bonn, Germany; Swiss Epilepsy Center (H.-J.H.), Zurich, Switzerland; Department of Psychiatry and Psychotherapy (H.J.), University Medical Center Hamburg-Eppendorf, Hamburg; AMEOS Klinikum (H.J.), Heiligenhafen; Department of Psychiatry and Psychotherapy (J. Kornhuber, J.M.M.), Friedrich-Alexander-University of Erlangen-Nuremberg, Erlangen; Department of Psychiatry and Psychotherapy (M.L.), University of Würzburg; Department of Neurology (J.P.), University of Rostock; DZNE (J.P.), Rostock; Department of Neurodegenerative Diseases and Geriatric Psychiatry (A.S.), University Hospital Bonn; DZNE (A.S.), Bonn; Institute of Human Genetics (A.E.V.), University Medical Center Hamburg-Eppendorf, Hamburg; Department of Psychiatry and Psychotherapy (J.W.), University Medical Center Göttingen; DZNE (J.W.), Göttingen, Germany; iBiMED (J.W.), Medical Sciences Department, University of Aveiro, Portugal; Clinic for Cognitive Neurology (M.L.S.), University Clinic Leipzig; and Max Planck Institute for Human Cognitive and Brain Sciences (M.L.S.), Leipzig, Germany. markus.otto@uni-ulm.de.

PMID: 30209235
DOI: 10.1212/WNL.0000000000006318

Abstract

Objective: To determine the association of serum neurofilament light chain (NfL) with functional deterioration and brain atrophy during follow-up of patients with behavioral variant frontotemporal dementia (bvFTD).

Methods: Blood NfL levels from 74 patients with bvFTD, 26 with Alzheimer disease (AD), 17 with mild cognitive impairment (MCI), and 15 healthy controls (Con) at baseline and follow-up were determined and analyzed for the diagnostic potential in relation to functional assessment (Clinical Dementia Rating Scale Sum of Boxes [CDR-SOB], frontotemporal lobar degeneration-related CDR-SOB, Mini-Mental State Examination [MMSE]) and brain volumetry.

Results: At baseline, serum NfL level correlated with CSF NfL (bvFTD r = 0.706, p < 0.0001; AD/MCI r = 0.666, p = 0.0003). Highest serum levels were observed in bvFTD (p <0 0.0001 vs Con and MCI, p = 0.0078 vs AD, respectively). Discrimination of bvFTD from Con/MCI/AD was possible with 91%/74%/74% sensitivity and 79%/74%/58% specificity. At follow-up, serum NfL increased in bvFTD and AD (p = 0.0039 and p = 0.0006, respectively). At baseline and follow-up, NfL correlated with functional scores of patients with bvFTD (e.g., CDR-SOB [baseline] r = 0.4157, p = 0.0006; [follow-up] r = 0.5629, p < 0.0001) and with atrophy in the gray and white matter of many brain regions including frontal and subcortical areas (e.g., frontal lobe: r = -0.5857, p < 0.0001; 95% confidence interval -0.7415 to -0.3701). For patients with AD/MCI, NfL correlated with the functional performance as well (e.g., CDR-SOB [baseline] r = 0.6624, p < 0.0001; [follow-up] r = 0.5659, p = 0.0003) but not with regional brain volumes.

Conclusions: As serum NfL correlates with functional impairment and brain atrophy in bvFTD at different disease stages, we propose it as marker of disease severity, paving the way for its future use as outcome measure for clinical trials.

Classification of evidence: This study provides Class III evidence that for patients with cognitive problems, serum NfL concentration discriminates bvFTD from other forms of dementia.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Aged
Alzheimer Disease / blood
Alzheimer Disease / cerebrospinal fluid
Alzheimer Disease / diagnostic imaging
Alzheimer Disease / genetics
Atrophy
Biomarkers / blood
Biomarkers / cerebrospinal fluid
Brain / pathology
Cognitive Dysfunction / blood
Cognitive Dysfunction / cerebrospinal fluid
Cognitive Dysfunction / diagnostic imaging
Cognitive Dysfunction / genetics
Diagnosis, Differential
Disease Progression
Female
Follow-Up Studies
Frontotemporal Dementia / blood*
Frontotemporal Dementia / diagnostic imaging
Frontotemporal Dementia / genetics
Frontotemporal Dementia / pathology
Humans
Male
Middle Aged
Mutation
Neurofilament Proteins / blood*
Organ Size
Prospective Studies

Substances

Biomarkers
Neurofilament Proteins
neurofilament protein L