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

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Different CSF protein profiles in amyotrophic lateral sclerosis and frontotemporal dementia with C9orf72 hexanucleotide repeat expansion. / Barschke, Peggy; Öckl, Patrick; Steinacker, Petra; Al Shweiki, Mhd Rami; Weishaupt, Jochen H; Landwehrmeyer, G Bernhard; Anderl-Straub, Sarah; Weydt, Patrick; Diehl-Schmid, Janine; Danek, Adrian; Kornhuber, Johannes; Schroeter, Matthias L; Prudlo, Johannes; Jahn, Holger; Fassbender, Klaus; Lauer, Martin; van der Ende, Emma Louise; van Swieten, John Cornelis; Volk, Alexander E; Ludolph, Albert C; Otto, Markus; German FTLD Consortium.

In: J NEUROL NEUROSUR PS, Vol. 91, No. 5, 05.2020, p. 503-511.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Barschke, P, Öckl, P, Steinacker, P, Al Shweiki, MR, Weishaupt, JH, Landwehrmeyer, GB, Anderl-Straub, S, Weydt, P, Diehl-Schmid, J, Danek, A, Kornhuber, J, Schroeter, ML, Prudlo, J, Jahn, H, Fassbender, K, Lauer, M, van der Ende, EL, van Swieten, JC, Volk, AE, Ludolph, AC, Otto, M & German FTLD Consortium 2020, 'Different CSF protein profiles in amyotrophic lateral sclerosis and frontotemporal dementia with C9orf72 hexanucleotide repeat expansion', J NEUROL NEUROSUR PS, vol. 91, no. 5, pp. 503-511. https://doi.org/10.1136/jnnp-2019-322476

APA

Barschke, P., Öckl, P., Steinacker, P., Al Shweiki, M. R., Weishaupt, J. H., Landwehrmeyer, G. B., Anderl-Straub, S., Weydt, P., Diehl-Schmid, J., Danek, A., Kornhuber, J., Schroeter, M. L., Prudlo, J., Jahn, H., Fassbender, K., Lauer, M., van der Ende, E. L., van Swieten, J. C., Volk, A. E., ... German FTLD Consortium (2020). Different CSF protein profiles in amyotrophic lateral sclerosis and frontotemporal dementia with C9orf72 hexanucleotide repeat expansion. J NEUROL NEUROSUR PS, 91(5), 503-511. https://doi.org/10.1136/jnnp-2019-322476

Vancouver

Barschke P, Öckl P, Steinacker P, Al Shweiki MR, Weishaupt JH, Landwehrmeyer GB et al. Different CSF protein profiles in amyotrophic lateral sclerosis and frontotemporal dementia with C9orf72 hexanucleotide repeat expansion. J NEUROL NEUROSUR PS. 2020 May;91(5):503-511. https://doi.org/10.1136/jnnp-2019-322476

Bibtex

@article{e23af5b2abf84a5b919eda94def48968,
title = "Different CSF protein profiles in amyotrophic lateral sclerosis and frontotemporal dementia with C9orf72 hexanucleotide repeat expansion",
abstract = "OBJECTIVES: 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.METHODS: 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).RESULTS: 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 pentraxin receptor (NPTXR) levels in C9-FTD versus CAR.CONCLUSIONS: This study presents a deep proteomic CSF analysis of C9-ALS versus C9-FTD patients. As a proof of concept, we observed higher NEFM and CHIT1 CSF levels in C9-ALS. In addition, we also show clear upregulation of UCHL1 in C9-ALS and downregulation of NPTXR in C9-FTD. Significant differences in UCHL1 CSF levels may explain diverging ubiquitination and autophagy processes and NPTXR levels might reflect different synapses organisation processes.",
author = "Peggy Barschke and Patrick {\"O}ckl and Petra Steinacker and {Al Shweiki}, {Mhd Rami} and Weishaupt, {Jochen H} and Landwehrmeyer, {G Bernhard} and Sarah Anderl-Straub and Patrick Weydt and Janine Diehl-Schmid and Adrian Danek and Johannes Kornhuber and Schroeter, {Matthias L} and Johannes Prudlo and Holger Jahn and Klaus Fassbender and Martin Lauer and {van der Ende}, {Emma Louise} and {van Swieten}, {John Cornelis} and Volk, {Alexander E} and Ludolph, {Albert C} and Markus Otto and {German FTLD Consortium}",
note = "{\textcopyright} Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.",
year = "2020",
month = may,
doi = "10.1136/jnnp-2019-322476",
language = "English",
volume = "91",
pages = "503--511",
journal = "J NEUROL NEUROSUR PS",
issn = "0022-3050",
publisher = "BMJ PUBLISHING GROUP",
number = "5",

}

RIS

TY - JOUR

T1 - Different CSF protein profiles in amyotrophic lateral sclerosis and frontotemporal dementia with C9orf72 hexanucleotide repeat expansion

AU - Barschke, Peggy

AU - Öckl, Patrick

AU - Steinacker, Petra

AU - Al Shweiki, Mhd Rami

AU - Weishaupt, Jochen H

AU - Landwehrmeyer, G Bernhard

AU - Anderl-Straub, Sarah

AU - Weydt, Patrick

AU - Diehl-Schmid, Janine

AU - Danek, Adrian

AU - Kornhuber, Johannes

AU - Schroeter, Matthias L

AU - Prudlo, Johannes

AU - Jahn, Holger

AU - Fassbender, Klaus

AU - Lauer, Martin

AU - van der Ende, Emma Louise

AU - van Swieten, John Cornelis

AU - Volk, Alexander E

AU - Ludolph, Albert C

AU - Otto, Markus

AU - German FTLD Consortium

N1 - © Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.

PY - 2020/5

Y1 - 2020/5

N2 - OBJECTIVES: 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.METHODS: 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).RESULTS: 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 pentraxin receptor (NPTXR) levels in C9-FTD versus CAR.CONCLUSIONS: This study presents a deep proteomic CSF analysis of C9-ALS versus C9-FTD patients. As a proof of concept, we observed higher NEFM and CHIT1 CSF levels in C9-ALS. In addition, we also show clear upregulation of UCHL1 in C9-ALS and downregulation of NPTXR in C9-FTD. Significant differences in UCHL1 CSF levels may explain diverging ubiquitination and autophagy processes and NPTXR levels might reflect different synapses organisation processes.

AB - OBJECTIVES: 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.METHODS: 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).RESULTS: 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 pentraxin receptor (NPTXR) levels in C9-FTD versus CAR.CONCLUSIONS: This study presents a deep proteomic CSF analysis of C9-ALS versus C9-FTD patients. As a proof of concept, we observed higher NEFM and CHIT1 CSF levels in C9-ALS. In addition, we also show clear upregulation of UCHL1 in C9-ALS and downregulation of NPTXR in C9-FTD. Significant differences in UCHL1 CSF levels may explain diverging ubiquitination and autophagy processes and NPTXR levels might reflect different synapses organisation processes.

U2 - 10.1136/jnnp-2019-322476

DO - 10.1136/jnnp-2019-322476

M3 - SCORING: Journal article

C2 - 32132225

VL - 91

SP - 503

EP - 511

JO - J NEUROL NEUROSUR PS

JF - J NEUROL NEUROSUR PS

SN - 0022-3050

IS - 5

ER -