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Author Notes:

To whom correspondence should be addressed: Leonard Petrucelli, PhD, Department of Neuroscience, Mayo Clinic Florida, Telephone number: +1 904-953-2855, Fax number: +1 904-953-6276, Petrucelli.Leonard@mayo.edu, Tania Gendron, PhD, Department of Neuroscience, Mayo Clinic Florida, Telephone number: +1 904-953-6414, Fax number: +1 904-953-6276, Gendron.Tania@mayo.edu.

K.B.B., T.F.G., A.J., and L.P. contributed to the conception and design of the study.

T.F.G., L.M.D., M.G.H., N.N.D., J.W., T.M.M., P.P., J.Q.T., M.G., J.D.B., W.T.H., A.R., M.B., V.S., J.D.G., M.K.F., and K.B.B. contributed to the acquisition and analysis of data.

T.F.G. and M.G.H. drafted the text and prepared figures.

Members of the C9ORF72 Neurofilament Study Group participated in the collection of patient samples and data (Supplementary Table 1).

We are grateful to all patients who donated samples, and to the NIH centers and programs that made this possible.

We thank Jiyan An at Iron Horse Diagnostics, Inc. for expert technical guidance, Ted Hyman for sample processing at Washington University, and Jennifer Farren for study coordination at NINDS.

A.J. receives a salary from, and holds stock options with, Iron Horse Diagnostics, Inc..

T.F.G. and L.P. have a US patent on methods and materials for detecting C9ORF72-associated ALS and FTD using poly(GP) proteins (European patent filed).


Research Funding:

This work was supported in part by the National Institutes of Health (NIH)/National Institute on Aging [P01AG017586 (M.G., J.Q.T.), K23AG042856 (W.T.H.), P30AG10124 (J.Q.T., M.G.)]; NIH/National Institute of Neurological Disorders and Stroke [R21NS089979 (K.B.B., T.F.G.), R01NS078398 (T.M.M.), R35NS097273 (L.P.), R21NS084528 (L.P.), P01NS084974 (L.P., K.B.B.), R01NS088689 (L.P.), R01NS093865 (L.P.)]; Intramural NIH/National Institute of Neurological Disorders and Stroke [Z01NS003146 (M.K.F.)]; Department of Defense [ALSRP AL130125 (L.P.)]; Mayo Clinic Foundation (L.P.); Mayo Clinic Center for Individualized Medicine (K.B.B., T.F.G., L.P.); Amyotrophic Lateral Sclerosis Association (K.B.B., M.B, J.D.G., T.F.G., L.P., J.W.); Robert Packard Center for ALS Research at Johns Hopkins (L.P.); Target ALS (L.P.); Association for Frontotemporal Degeneration (L.P.); ALS Therapy Alliance (J.D.B., J.D.G); ALS Finding A Cure Foundation (J.D.B.); Muscular Dystrophy Association (#416137, T.F.G.; #4365 and #172123, M.B., J.W.); Italian Ministry of Health (RF-2013-02355764, A.R., V.S.) and STRENGTH project funded by EU Joint Programme – Neurodegenerative (A.R., V.S.); and CReATe (U54-NS-092091, M.B, J.W.), which is part of the Rare Diseases Clinical Research Network (RDCRN), an initiative of the Office of Rare Diseases Research (ORDR), NCATS.

CReATe is funded through collaboration between NCATS and NINDS


  • Science & Technology
  • Life Sciences & Biomedicine
  • Clinical Neurology
  • Neurosciences
  • Neurosciences & Neurology
  • C9ORF72
  • ALS
  • CSF

Phosphorylated Neurofilament Heavy Chain: A Biomarker of Survival for C9ORF72-Associated Amyotrophic Lateral Sclerosis

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Journal Title:

Annals of Neurology


Volume 82, Number 1


, Pages 139-146

Type of Work:

Article | Post-print: After Peer Review


As potential treatments for C9ORF72-associated amyotrophic lateral sclerosis (c9ALS) approach clinical trials, the identification of prognostic biomarkers for c9ALS becomes a priority. We show that levels of phosphorylated neurofilament heavy chain (pNFH) in cerebrospinal fluid (CSF) predict disease status and survival in c9ALS patients, and are largely stable over time. Moreover, c9ALS patients exhibit higher pNFH levels, more rapid disease progression, and shorter survival after disease onset than ALS patients without C9ORF72 expansions. These data support the use of CSF pNFH as a prognostic biomarker for clinical trials, which will increase the likelihood of successfully developing a treatment for c9ALS. Ann Neurol 2017;82:139–146.

Copyright information:

© 2017 The Authors Annals of Neurology published by Wiley Periodicals, Inc. on behalf of American Neurological Association

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