Muscle and not neuronal biomarkers correlate with severity in spinal and bulbar muscular atrophy.


Journal

Neurology
ISSN: 1526-632X
Titre abrégé: Neurology
Pays: United States
ID NLM: 0401060

Informations de publication

Date de publication:
12 03 2019
Historique:
received: 12 08 2018
accepted: 05 11 2018
pubmed: 23 2 2019
medline: 18 12 2019
entrez: 22 2 2019
Statut: ppublish

Résumé

To determine whether blood biomarkers of neuronal damage (neurofilament light chain [NfL]), muscle damage (creatine kinase [CK]), and muscle mass (creatinine) are altered in spinal and bulbar muscular atrophy (SBMA) and can be used as biomarkers for disease severity. In this multicenter longitudinal prospective study, plasma and serum were collected from 2 cohorts of patients with SBMA in London, United Kingdom (n = 50), and Padova, Italy (n = 43), along with disease (amyotrophic lateral sclerosis [ALS]) and healthy controls, and levels of plasma and serum NfL, CK, and creatinine were measured. Disease severity was assessed by the SBMA Functional Rating Scale and the Adult Myopathy Assessment Tool at baseline and 12 and 24 months. Blood NfL concentrations were increased in ALS samples, but were unchanged in both SBMA cohorts, were stable after 12 and 24 months, and were not correlated with clinical severity. Normal NfL levels were also found in a well-established mouse model of SBMA. Conversely, CK concentrations were significantly raised in SBMA compared with ALS samples, and were not correlated to the clinical measures. Creatinine concentrations were significantly reduced in SBMA, and strongly and significantly correlated with disease severity. While muscle damage and muscle mass biomarkers are abnormal in SBMA, axonal damage markers are unchanged, highlighting the relevant primary role of skeletal muscle in disease pathogenesis. Creatinine, but not CK, correlated with disease severity, confirming its role as a valuable biomarker in SBMA.

Identifiants

pubmed: 30787165
pii: WNL.0000000000007097
doi: 10.1212/WNL.0000000000007097
pmc: PMC6511101
doi:

Substances chimiques

Biomarkers 0
Neurofilament Proteins 0
neurofilament protein L 0
Creatinine AYI8EX34EU
Creatine Kinase EC 2.7.3.2

Types de publication

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

Langues

eng

Sous-ensembles de citation

IM

Pagination

e1205-e1211

Subventions

Organisme : Medical Research Council
ID : MR/M008606/1
Pays : United Kingdom
Organisme : Motor Neurone Disease Association
ID : FRATTA/JAN15/946-795
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/S006508/1
Pays : United Kingdom
Organisme : Motor Neurone Disease Association
ID : MALASPINA/APR13/817-791
Pays : United Kingdom
Organisme : Motor Neurone Disease Association
ID : TURNER/OCT15/972-797
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 205162/Z/16/Z
Pays : United Kingdom

Commentaires et corrections

Type : ErratumIn

Informations de copyright

Copyright © 2019 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.

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Auteurs

Vittoria Lombardi (V)

From the Institute of Neurology (V.L., O.J.Z., L.Z., C.H., M.F., C.-H.L., B.M., H.Z., A.H., L.G., M.H., P.F.), University College London Institute of Neurology, Queen Square, London; Blizard Institute (V.L., A.M.), Queen Mary, University of London, UK; Department of Neurosciences (G.Q., I.M., C.B., G.S.), University of Padova, Italy; Department of Neurology (C.-H.L.), China Medical University Hospital, Taiwan; Basildon Hospital (K.A.), UK; Department of Physiology, Anatomy and Genetics (C.R.), University of Oxford; UK Dementia Research Institute at UCL (H.Z., A.H.), London, UK; Clinical Neurochemistry Laboratory (H.Z.), Sahlgrenska University Hospital; and the Department of Psychiatry and Neurochemistry (H.Z.), Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.

Giorgia Querin (G)

From the Institute of Neurology (V.L., O.J.Z., L.Z., C.H., M.F., C.-H.L., B.M., H.Z., A.H., L.G., M.H., P.F.), University College London Institute of Neurology, Queen Square, London; Blizard Institute (V.L., A.M.), Queen Mary, University of London, UK; Department of Neurosciences (G.Q., I.M., C.B., G.S.), University of Padova, Italy; Department of Neurology (C.-H.L.), China Medical University Hospital, Taiwan; Basildon Hospital (K.A.), UK; Department of Physiology, Anatomy and Genetics (C.R.), University of Oxford; UK Dementia Research Institute at UCL (H.Z., A.H.), London, UK; Clinical Neurochemistry Laboratory (H.Z.), Sahlgrenska University Hospital; and the Department of Psychiatry and Neurochemistry (H.Z.), Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.

Oliver J Ziff (OJ)

From the Institute of Neurology (V.L., O.J.Z., L.Z., C.H., M.F., C.-H.L., B.M., H.Z., A.H., L.G., M.H., P.F.), University College London Institute of Neurology, Queen Square, London; Blizard Institute (V.L., A.M.), Queen Mary, University of London, UK; Department of Neurosciences (G.Q., I.M., C.B., G.S.), University of Padova, Italy; Department of Neurology (C.-H.L.), China Medical University Hospital, Taiwan; Basildon Hospital (K.A.), UK; Department of Physiology, Anatomy and Genetics (C.R.), University of Oxford; UK Dementia Research Institute at UCL (H.Z., A.H.), London, UK; Clinical Neurochemistry Laboratory (H.Z.), Sahlgrenska University Hospital; and the Department of Psychiatry and Neurochemistry (H.Z.), Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.

Luca Zampedri (L)

From the Institute of Neurology (V.L., O.J.Z., L.Z., C.H., M.F., C.-H.L., B.M., H.Z., A.H., L.G., M.H., P.F.), University College London Institute of Neurology, Queen Square, London; Blizard Institute (V.L., A.M.), Queen Mary, University of London, UK; Department of Neurosciences (G.Q., I.M., C.B., G.S.), University of Padova, Italy; Department of Neurology (C.-H.L.), China Medical University Hospital, Taiwan; Basildon Hospital (K.A.), UK; Department of Physiology, Anatomy and Genetics (C.R.), University of Oxford; UK Dementia Research Institute at UCL (H.Z., A.H.), London, UK; Clinical Neurochemistry Laboratory (H.Z.), Sahlgrenska University Hospital; and the Department of Psychiatry and Neurochemistry (H.Z.), Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.

Ilaria Martinelli (I)

From the Institute of Neurology (V.L., O.J.Z., L.Z., C.H., M.F., C.-H.L., B.M., H.Z., A.H., L.G., M.H., P.F.), University College London Institute of Neurology, Queen Square, London; Blizard Institute (V.L., A.M.), Queen Mary, University of London, UK; Department of Neurosciences (G.Q., I.M., C.B., G.S.), University of Padova, Italy; Department of Neurology (C.-H.L.), China Medical University Hospital, Taiwan; Basildon Hospital (K.A.), UK; Department of Physiology, Anatomy and Genetics (C.R.), University of Oxford; UK Dementia Research Institute at UCL (H.Z., A.H.), London, UK; Clinical Neurochemistry Laboratory (H.Z.), Sahlgrenska University Hospital; and the Department of Psychiatry and Neurochemistry (H.Z.), Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.

Carolin Heller (C)

From the Institute of Neurology (V.L., O.J.Z., L.Z., C.H., M.F., C.-H.L., B.M., H.Z., A.H., L.G., M.H., P.F.), University College London Institute of Neurology, Queen Square, London; Blizard Institute (V.L., A.M.), Queen Mary, University of London, UK; Department of Neurosciences (G.Q., I.M., C.B., G.S.), University of Padova, Italy; Department of Neurology (C.-H.L.), China Medical University Hospital, Taiwan; Basildon Hospital (K.A.), UK; Department of Physiology, Anatomy and Genetics (C.R.), University of Oxford; UK Dementia Research Institute at UCL (H.Z., A.H.), London, UK; Clinical Neurochemistry Laboratory (H.Z.), Sahlgrenska University Hospital; and the Department of Psychiatry and Neurochemistry (H.Z.), Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.

Martha Foiani (M)

From the Institute of Neurology (V.L., O.J.Z., L.Z., C.H., M.F., C.-H.L., B.M., H.Z., A.H., L.G., M.H., P.F.), University College London Institute of Neurology, Queen Square, London; Blizard Institute (V.L., A.M.), Queen Mary, University of London, UK; Department of Neurosciences (G.Q., I.M., C.B., G.S.), University of Padova, Italy; Department of Neurology (C.-H.L.), China Medical University Hospital, Taiwan; Basildon Hospital (K.A.), UK; Department of Physiology, Anatomy and Genetics (C.R.), University of Oxford; UK Dementia Research Institute at UCL (H.Z., A.H.), London, UK; Clinical Neurochemistry Laboratory (H.Z.), Sahlgrenska University Hospital; and the Department of Psychiatry and Neurochemistry (H.Z.), Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.

Cinzia Bertolin (C)

From the Institute of Neurology (V.L., O.J.Z., L.Z., C.H., M.F., C.-H.L., B.M., H.Z., A.H., L.G., M.H., P.F.), University College London Institute of Neurology, Queen Square, London; Blizard Institute (V.L., A.M.), Queen Mary, University of London, UK; Department of Neurosciences (G.Q., I.M., C.B., G.S.), University of Padova, Italy; Department of Neurology (C.-H.L.), China Medical University Hospital, Taiwan; Basildon Hospital (K.A.), UK; Department of Physiology, Anatomy and Genetics (C.R.), University of Oxford; UK Dementia Research Institute at UCL (H.Z., A.H.), London, UK; Clinical Neurochemistry Laboratory (H.Z.), Sahlgrenska University Hospital; and the Department of Psychiatry and Neurochemistry (H.Z.), Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.

Ching-Hua Lu (CH)

From the Institute of Neurology (V.L., O.J.Z., L.Z., C.H., M.F., C.-H.L., B.M., H.Z., A.H., L.G., M.H., P.F.), University College London Institute of Neurology, Queen Square, London; Blizard Institute (V.L., A.M.), Queen Mary, University of London, UK; Department of Neurosciences (G.Q., I.M., C.B., G.S.), University of Padova, Italy; Department of Neurology (C.-H.L.), China Medical University Hospital, Taiwan; Basildon Hospital (K.A.), UK; Department of Physiology, Anatomy and Genetics (C.R.), University of Oxford; UK Dementia Research Institute at UCL (H.Z., A.H.), London, UK; Clinical Neurochemistry Laboratory (H.Z.), Sahlgrenska University Hospital; and the Department of Psychiatry and Neurochemistry (H.Z.), Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.

Bilal Malik (B)

From the Institute of Neurology (V.L., O.J.Z., L.Z., C.H., M.F., C.-H.L., B.M., H.Z., A.H., L.G., M.H., P.F.), University College London Institute of Neurology, Queen Square, London; Blizard Institute (V.L., A.M.), Queen Mary, University of London, UK; Department of Neurosciences (G.Q., I.M., C.B., G.S.), University of Padova, Italy; Department of Neurology (C.-H.L.), China Medical University Hospital, Taiwan; Basildon Hospital (K.A.), UK; Department of Physiology, Anatomy and Genetics (C.R.), University of Oxford; UK Dementia Research Institute at UCL (H.Z., A.H.), London, UK; Clinical Neurochemistry Laboratory (H.Z.), Sahlgrenska University Hospital; and the Department of Psychiatry and Neurochemistry (H.Z.), Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.

Kezia Allen (K)

From the Institute of Neurology (V.L., O.J.Z., L.Z., C.H., M.F., C.-H.L., B.M., H.Z., A.H., L.G., M.H., P.F.), University College London Institute of Neurology, Queen Square, London; Blizard Institute (V.L., A.M.), Queen Mary, University of London, UK; Department of Neurosciences (G.Q., I.M., C.B., G.S.), University of Padova, Italy; Department of Neurology (C.-H.L.), China Medical University Hospital, Taiwan; Basildon Hospital (K.A.), UK; Department of Physiology, Anatomy and Genetics (C.R.), University of Oxford; UK Dementia Research Institute at UCL (H.Z., A.H.), London, UK; Clinical Neurochemistry Laboratory (H.Z.), Sahlgrenska University Hospital; and the Department of Psychiatry and Neurochemistry (H.Z.), Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.

Carlo Rinaldi (C)

From the Institute of Neurology (V.L., O.J.Z., L.Z., C.H., M.F., C.-H.L., B.M., H.Z., A.H., L.G., M.H., P.F.), University College London Institute of Neurology, Queen Square, London; Blizard Institute (V.L., A.M.), Queen Mary, University of London, UK; Department of Neurosciences (G.Q., I.M., C.B., G.S.), University of Padova, Italy; Department of Neurology (C.-H.L.), China Medical University Hospital, Taiwan; Basildon Hospital (K.A.), UK; Department of Physiology, Anatomy and Genetics (C.R.), University of Oxford; UK Dementia Research Institute at UCL (H.Z., A.H.), London, UK; Clinical Neurochemistry Laboratory (H.Z.), Sahlgrenska University Hospital; and the Department of Psychiatry and Neurochemistry (H.Z.), Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.

Henrik Zetterberg (H)

From the Institute of Neurology (V.L., O.J.Z., L.Z., C.H., M.F., C.-H.L., B.M., H.Z., A.H., L.G., M.H., P.F.), University College London Institute of Neurology, Queen Square, London; Blizard Institute (V.L., A.M.), Queen Mary, University of London, UK; Department of Neurosciences (G.Q., I.M., C.B., G.S.), University of Padova, Italy; Department of Neurology (C.-H.L.), China Medical University Hospital, Taiwan; Basildon Hospital (K.A.), UK; Department of Physiology, Anatomy and Genetics (C.R.), University of Oxford; UK Dementia Research Institute at UCL (H.Z., A.H.), London, UK; Clinical Neurochemistry Laboratory (H.Z.), Sahlgrenska University Hospital; and the Department of Psychiatry and Neurochemistry (H.Z.), Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.

Amanda Heslegrave (A)

From the Institute of Neurology (V.L., O.J.Z., L.Z., C.H., M.F., C.-H.L., B.M., H.Z., A.H., L.G., M.H., P.F.), University College London Institute of Neurology, Queen Square, London; Blizard Institute (V.L., A.M.), Queen Mary, University of London, UK; Department of Neurosciences (G.Q., I.M., C.B., G.S.), University of Padova, Italy; Department of Neurology (C.-H.L.), China Medical University Hospital, Taiwan; Basildon Hospital (K.A.), UK; Department of Physiology, Anatomy and Genetics (C.R.), University of Oxford; UK Dementia Research Institute at UCL (H.Z., A.H.), London, UK; Clinical Neurochemistry Laboratory (H.Z.), Sahlgrenska University Hospital; and the Department of Psychiatry and Neurochemistry (H.Z.), Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.

Linda Greensmith (L)

From the Institute of Neurology (V.L., O.J.Z., L.Z., C.H., M.F., C.-H.L., B.M., H.Z., A.H., L.G., M.H., P.F.), University College London Institute of Neurology, Queen Square, London; Blizard Institute (V.L., A.M.), Queen Mary, University of London, UK; Department of Neurosciences (G.Q., I.M., C.B., G.S.), University of Padova, Italy; Department of Neurology (C.-H.L.), China Medical University Hospital, Taiwan; Basildon Hospital (K.A.), UK; Department of Physiology, Anatomy and Genetics (C.R.), University of Oxford; UK Dementia Research Institute at UCL (H.Z., A.H.), London, UK; Clinical Neurochemistry Laboratory (H.Z.), Sahlgrenska University Hospital; and the Department of Psychiatry and Neurochemistry (H.Z.), Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.

Michael Hanna (M)

From the Institute of Neurology (V.L., O.J.Z., L.Z., C.H., M.F., C.-H.L., B.M., H.Z., A.H., L.G., M.H., P.F.), University College London Institute of Neurology, Queen Square, London; Blizard Institute (V.L., A.M.), Queen Mary, University of London, UK; Department of Neurosciences (G.Q., I.M., C.B., G.S.), University of Padova, Italy; Department of Neurology (C.-H.L.), China Medical University Hospital, Taiwan; Basildon Hospital (K.A.), UK; Department of Physiology, Anatomy and Genetics (C.R.), University of Oxford; UK Dementia Research Institute at UCL (H.Z., A.H.), London, UK; Clinical Neurochemistry Laboratory (H.Z.), Sahlgrenska University Hospital; and the Department of Psychiatry and Neurochemistry (H.Z.), Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.

Gianni Soraru (G)

From the Institute of Neurology (V.L., O.J.Z., L.Z., C.H., M.F., C.-H.L., B.M., H.Z., A.H., L.G., M.H., P.F.), University College London Institute of Neurology, Queen Square, London; Blizard Institute (V.L., A.M.), Queen Mary, University of London, UK; Department of Neurosciences (G.Q., I.M., C.B., G.S.), University of Padova, Italy; Department of Neurology (C.-H.L.), China Medical University Hospital, Taiwan; Basildon Hospital (K.A.), UK; Department of Physiology, Anatomy and Genetics (C.R.), University of Oxford; UK Dementia Research Institute at UCL (H.Z., A.H.), London, UK; Clinical Neurochemistry Laboratory (H.Z.), Sahlgrenska University Hospital; and the Department of Psychiatry and Neurochemistry (H.Z.), Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.

Andrea Malaspina (A)

From the Institute of Neurology (V.L., O.J.Z., L.Z., C.H., M.F., C.-H.L., B.M., H.Z., A.H., L.G., M.H., P.F.), University College London Institute of Neurology, Queen Square, London; Blizard Institute (V.L., A.M.), Queen Mary, University of London, UK; Department of Neurosciences (G.Q., I.M., C.B., G.S.), University of Padova, Italy; Department of Neurology (C.-H.L.), China Medical University Hospital, Taiwan; Basildon Hospital (K.A.), UK; Department of Physiology, Anatomy and Genetics (C.R.), University of Oxford; UK Dementia Research Institute at UCL (H.Z., A.H.), London, UK; Clinical Neurochemistry Laboratory (H.Z.), Sahlgrenska University Hospital; and the Department of Psychiatry and Neurochemistry (H.Z.), Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden. p.fratta@ucl.ac.uk a.malaspina@qmul.ac.uk.

Pietro Fratta (P)

From the Institute of Neurology (V.L., O.J.Z., L.Z., C.H., M.F., C.-H.L., B.M., H.Z., A.H., L.G., M.H., P.F.), University College London Institute of Neurology, Queen Square, London; Blizard Institute (V.L., A.M.), Queen Mary, University of London, UK; Department of Neurosciences (G.Q., I.M., C.B., G.S.), University of Padova, Italy; Department of Neurology (C.-H.L.), China Medical University Hospital, Taiwan; Basildon Hospital (K.A.), UK; Department of Physiology, Anatomy and Genetics (C.R.), University of Oxford; UK Dementia Research Institute at UCL (H.Z., A.H.), London, UK; Clinical Neurochemistry Laboratory (H.Z.), Sahlgrenska University Hospital; and the Department of Psychiatry and Neurochemistry (H.Z.), Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden. p.fratta@ucl.ac.uk a.malaspina@qmul.ac.uk.

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