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

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Poly-GP in cerebrospinal fluid links C9orf72-associated dipeptide repeat expression to the asymptomatic phase of ALS/FTD. / Lehmer, Carina; Oeckl, Patrick; Weishaupt, Jochen H; Volk, Alexander E; Diehl-Schmid, Janine; Schroeter, Matthias L; Lauer, Martin; Kornhuber, Johannes; Levin, Johannes; Fassbender, Klaus; Landwehrmeyer, Bernhard; Schludi, Martin H; Arzberger, Thomas; Kremmer, Elisabeth; Flatley, Andrew; Feederle, Regina; Steinacker, Petra; Weydt, Patrick; Ludolph, Albert C; Edbauer, Dieter; Otto, Markus; German Consortium for Frontotemporal Lobar Degeneration.

In: EMBO MOL MED, Vol. 9, No. 7, 07.2017, p. 859-868.

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

Harvard

Lehmer, C, Oeckl, P, Weishaupt, JH, Volk, AE, Diehl-Schmid, J, Schroeter, ML, Lauer, M, Kornhuber, J, Levin, J, Fassbender, K, Landwehrmeyer, B, Schludi, MH, Arzberger, T, Kremmer, E, Flatley, A, Feederle, R, Steinacker, P, Weydt, P, Ludolph, AC, Edbauer, D, Otto, M & German Consortium for Frontotemporal Lobar Degeneration 2017, 'Poly-GP in cerebrospinal fluid links C9orf72-associated dipeptide repeat expression to the asymptomatic phase of ALS/FTD', EMBO MOL MED, vol. 9, no. 7, pp. 859-868. https://doi.org/10.15252/emmm.201607486

APA

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., ... German Consortium for Frontotemporal Lobar Degeneration (2017). Poly-GP in cerebrospinal fluid links C9orf72-associated dipeptide repeat expression to the asymptomatic phase of ALS/FTD. EMBO MOL MED, 9(7), 859-868. https://doi.org/10.15252/emmm.201607486

Vancouver

Lehmer C, Oeckl P, Weishaupt JH, Volk AE, Diehl-Schmid J, Schroeter ML et al. Poly-GP in cerebrospinal fluid links C9orf72-associated dipeptide repeat expression to the asymptomatic phase of ALS/FTD. EMBO MOL MED. 2017 Jul;9(7):859-868. https://doi.org/10.15252/emmm.201607486

Bibtex

@article{0ec78cb4993443ada6ae8d0251b77602,
title = "Poly-GP in cerebrospinal fluid links C9orf72-associated dipeptide repeat expression to the asymptomatic phase of ALS/FTD",
abstract = "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.",
keywords = "Journal Article",
author = "Carina Lehmer and Patrick Oeckl and Weishaupt, {Jochen H} and Volk, {Alexander E} and Janine Diehl-Schmid and Schroeter, {Matthias L} and Martin Lauer and Johannes Kornhuber and Johannes Levin and Klaus Fassbender and Bernhard Landwehrmeyer and Schludi, {Martin H} and Thomas Arzberger and Elisabeth Kremmer and Andrew Flatley and Regina Feederle and Petra Steinacker and Patrick Weydt and Ludolph, {Albert C} and Dieter Edbauer and Markus Otto and {German Consortium for Frontotemporal Lobar Degeneration}",
note = "{\textcopyright} 2017 The Authors. Published under the terms of the CC BY 4.0 license.",
year = "2017",
month = jul,
doi = "10.15252/emmm.201607486",
language = "English",
volume = "9",
pages = "859--868",
journal = "EMBO MOL MED",
issn = "1757-4676",
publisher = "Wiley-Blackwell",
number = "7",

}

RIS

TY - JOUR

T1 - Poly-GP in cerebrospinal fluid links C9orf72-associated dipeptide repeat expression to the asymptomatic phase of ALS/FTD

AU - Lehmer, Carina

AU - Oeckl, Patrick

AU - Weishaupt, Jochen H

AU - Volk, Alexander E

AU - Diehl-Schmid, Janine

AU - Schroeter, Matthias L

AU - Lauer, Martin

AU - Kornhuber, Johannes

AU - Levin, Johannes

AU - Fassbender, Klaus

AU - Landwehrmeyer, Bernhard

AU - Schludi, Martin H

AU - Arzberger, Thomas

AU - Kremmer, Elisabeth

AU - Flatley, Andrew

AU - Feederle, Regina

AU - Steinacker, Petra

AU - Weydt, Patrick

AU - Ludolph, Albert C

AU - Edbauer, Dieter

AU - Otto, Markus

AU - German Consortium for Frontotemporal Lobar Degeneration

N1 - © 2017 The Authors. Published under the terms of the CC BY 4.0 license.

PY - 2017/7

Y1 - 2017/7

N2 - 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.

AB - 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.

KW - Journal Article

U2 - 10.15252/emmm.201607486

DO - 10.15252/emmm.201607486

M3 - SCORING: Journal article

C2 - 28408402

VL - 9

SP - 859

EP - 868

JO - EMBO MOL MED

JF - EMBO MOL MED

SN - 1757-4676

IS - 7

ER -