Journal
EMBO MOLECULAR MEDICINE
Volume 9, Issue 7, Pages 859-868Publisher
WILEY
DOI: 10.15252/emmm.201607486
Keywords
amyotrophic lateral sclerosis; biomarker; C9orf72; cerebrospinal fluid; frontotemporal dementia
Categories
Funding
- JPND network SOPHIA [01ED1202A]
- JPND network BiomarkAPD [01ED1203F]
- JPND network PreFrontAls [01ED1512]
- JPND network STRENGTH [01ED1408]
- German Federal Ministry of Education and Research [FTLDc O1GI1007A, MND-Net 01GM1103A]
- EU [NADINE 246513, FAIR-PARK II 633190, 617198]
- German research foundation/DFG [VO2028]
- foundation of the state Baden-Wurttemberg [D.3830]
- BIU [D.5009]
- Charcot Foundation
- NOMIS Foundation
Ask authors/readers for more resources
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available