Different CSF protein profiles in amyotrophic lateral sclerosis and frontotemporal dementia with C9orf72 hexanucleotide repeat expansion

Journal of Neurology, Neurosurgery, and Psychiatry
Peggy BarschkeGerman FTLD consortium

Abstract

The hexanucleotide repeat expansion in the C9orf72 gene is the most common mutation associated with amyotrophic lateral sclerosis (C9-ALS) and frontotemporal dementia (C9-FTD). Until now, it is unknown which factors define whether C9orf72 mutation carriers develop ALS or FTD. Our aim was to identify protein biomarker candidates in the cerebrospinal fluid (CSF) which differentiate between C9-ALS and C9-FTD and might be indicative for the outcome of the mutation. We compared the CSF proteome of 16 C9-ALS and 8 C9-FTD patients and 11 asymptomatic C9orf72 mutation carriers (CAR) by isobaric tags for relative and absolute quantitation. Eleven biomarker candidates were selected from the pool of differentially regulated proteins for further validation by multiple reaction monitoring and single-molecule array in a larger cohort (n=156). In total, 2095 CSF proteins were identified and 236 proteins were significantly different in C9-ALS versus C9-FTD including neurofilament medium polypeptide (NEFM) and chitotriosidase-1 (CHIT1). Eight candidates were successfully validated including significantly increased ubiquitin carboxyl-terminal hydrolase isozyme L1 (UCHL1) levels in C9-ALS compared with C9-FTD and controls and decreased neuronal p...Continue Reading

References

Jul 24, 2001·Amyotrophic Lateral Sclerosis and Other Motor Neuron Disorders : Official Publication of the World Federation of Neurology, Research Group on Motor Neuron Diseases·B R BrooksUNKNOWN World Federation of Neurology Research Group on Motor Neuron Diseases
Jan 29, 2005·Journal of Neuroscience Research·C Evrard, P Rouget
Oct 3, 2008·Brain : a Journal of Neurology·David S KnopmanNathaniel Mercaldo
Jan 23, 2009·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Suh Young JeongSamuel David
Nov 1, 2012·Human Mutation·Julie van der ZeeUNKNOWN European Early-Onset Dementia Consortium
Jan 4, 2013·Acta Neurologica Scandinavica. Supplementum·A C KroksveenF S Berven
Feb 11, 2014·Parkinsonism & Related Disorders·Stefania MondelloAndreas Jeromin
Aug 25, 2015·Journal of Neurology, Neurosurgery, and Psychiatry·Petra SteinackerMarkus Otto
Aug 6, 2016·Small GTPases·Camille Corbier, Chantal Sellier
Sep 30, 2016·Proceedings of the National Academy of Sciences of the United States of America·Chunxing YangZuoshang Xu
Nov 1, 2016·Nature Neuroscience·Rajeeve SivadasanMichael Sendtner
Dec 18, 2016·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Sung-Jin LeeThomas C Südhof
Apr 23, 2017·Journal of Molecular Biology·Daniel L Kober, Tom J Brett
Jan 14, 2018·Annals of Neurology·Alexander G ThompsonMartin R Turner
Sep 19, 2018·Journal of Neurology, Neurosurgery, and Psychiatry·Patrick OecklMarkus Otto
Oct 26, 2018·Journal of Neurology, Neurosurgery, and Psychiatry·Junhao WenUNKNOWN Predict to Prevent Frontotemporal Lobar Degeneration and Amyotrophic Lateral Sclerosis (PREV-DEMALS) Study Group
Apr 26, 2019·Annals of Clinical and Translational Neurology·Emma L van der EndeJohn C van Swieten
May 13, 2019·Journal of Neurology, Neurosurgery, and Psychiatry·Eduardo CaverzasiSuzee E Lee
Jun 27, 2019·OncoTargets and Therapy·JunFei ZhangLiShan Yang
Aug 16, 2019·Clinical Chemistry and Laboratory Medicine : CCLM·Bryant LimEleftherios P Diamandis

❮ Previous
Next ❯

Citations

Nov 15, 2020·Journal of Neurology, Neurosurgery, and Psychiatry·Imogen Joanna SwiftJonathan Daniel Rohrer
Nov 12, 2021·Expert Review of Proteomics·Alexander G ThompsonMartin R Turner

❮ Previous
Next ❯

Related Concepts

Related Feeds

ALS: Genetics

Amyotrophic Lateral Sclerosis (ALS) is a progressive neurodegenerative disorder characterized by muscle weakness. ALS is a genetically heterogeneous disorder with several causative genes. Here are the latest discoveries pertaining to the genetics of this disease.

ALS: Genetics

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder characterized by muscle weakness. Here is the latest research investigating genetic alterations in this genetically heterogeneous disorder.

CSF & Lymphatic System

This feed focuses on Cerebral Spinal Fluid (CSF) and the lymphatic system. Discover the latest papers using imaging techniques to track CSF outflow into the lymphatic system in animal models.

Amyloid Lateral Sclerosis

Amyotrophic Lateral Sclerosis (ALS) is a progressive nervous system disease associated with the death of neurons that control voluntary muscles. Discover the latest research on ALS here.

Autophagy & Model Organisms

Autophagy is a cellular process that allows degradation by the lysosome of cytoplasmic components such as proteins or organelles. Here is the latest research on autophagy & model organisms