PuSH - Publication Server of Helmholtz Zentrum München

Export: TXT Text RIS Endnote (RIS) BIB BibTeX
Lehmer, C.* ; Oeckl, P.* ; Weishaupt, J.H.* ; Volk, A.E.* ; Diehl-Schmid, J.* ; Schroeter, M.L.* ; Lauer, M.* ; Kornhuber, J.* ; Levin, J.* ; Fassbender, K.* ; Landwehrmeyer, B.* ; Schludi, M.H.* ; Arzberger, T.* ; Kremmer, E. ; Flatley, A. ; Feederle, R. ; Steinacker, P.* ; Weydt, P.* ; Ludolph, A.C.* ; Edbauer, D.* ; Otto, M.*

Poly-GP in cerebrospinal fluid links C9orf72-associated dipeptide repeat expression to the asymptomatic phase of ALS/FTD.

EMBO Mol. Med. 9, 859-868 (2017)
Publ. Version/Full Text Research data DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
The C9orf72 GGGGCC repeat expansion is a major cause of amyotrophic lateral sclerosis and frontotemporal dementia (c9ALS/FTD). Non-conventional repeat translation results in five dipeptide repeat proteins (DPRs), but their clinical utility, overall significance, and temporal course in the pathogenesis of c9ALS/FTD are unclear, although animal models support a gain-of-function mechanism. Here, we established a poly-GP immunoassay from cerebrospinal fluid (CSF) to identify and characterize C9orf72 patients. Significant poly-GP levels were already detectable in asymptomatic C9orf72 mutation carriers compared to healthy controls and patients with other neurodegenerative diseases. The poly-GP levels in asymptomatic carriers were similar to symptomatic c9ALS/FTD cases. Poly-GP levels were not correlated with disease onset, clinical scores, and CSF levels of neurofilaments as a marker for axonal damage. Poly-GP determination in CSF revealed a C9orf72 mutation carrier in our cohort and may thus be used as a diagnostic marker in addition to genetic testing to screen patients. Presymptomatic expression of poly-GP and likely other DPR species may contribute to disease onset and thus represents an alluring therapeutic target.
Impact Factor
Scopus SNIP
Web of Science
Times Cited
Scopus
Cited By
Altmetric
9.249
1.869
45
52
Tags
Annotations
Special Publikation
Hide on homepage

Edit extra information
Edit own tags
Private
Edit own annotation
Private
Hide on publication lists
on hompage
Mark as special
publikation
Publication type Article: Journal article
Document type Scientific Article
Keywords C9orf72 ; Amyotrophic Lateral Sclerosis ; Biomarker ; Cerebrospinal Fluid ; Frontotemporal Dementia; C9orf72 Hexanucleotide Repeat; Frontotemporal Dementia; Ggggcc-repeat; Clinicopathological Correlations; Antisense Transcripts; Rna Foci; Proteins; Expansions; Als; C9ftd/als
Language english
Publication Year 2017
HGF-reported in Year 2017
ISSN (print) / ISBN 1757-4676
e-ISSN 1757-4684
Journal EMBO Molecular Medicine
Quellenangaben Volume: 9, Issue: 7, Pages: 859-868 Article Number: , Supplement: ,
Publisher Wiley
Publishing Place Chichester
Reviewing status Peer reviewed
Institute(s) CF Monoclonal Antibodies (CF-MAB)
POF-Topic(s) 30504 - Mechanisms of Genetic and Environmental Influences on Health and Disease
30201 - Metabolic Health
Research field(s) Immune Response and Infection
Helmholtz Diabetes Center
PSP Element(s) G-501760-001
G-502210-001
DOI 10.15252/emmm.201607486
WOS ID WOS:000404552000003
Scopus ID 85017524397
PubMed ID 28408402
Erfassungsdatum 2017-06-26
[➜Report correction]