A panel of CSF proteins separates genetic frontotemporal dementia from presymptomatic mutation carriers: a GENFI study

Abstract Background A detailed understanding of the pathological processes involved in genetic frontotemporal dementia is critical in order to provide the patients with an optimal future treatment. Protein levels in CSF have the potential to reflect different pathophysiological processes in the brai...

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Autores principales:	Sofia Bergström, Linn Öijerstedt, Julia Remnestål, Jennie Olofsson, Abbe Ullgren, Harro Seelaar, John C. van Swieten, Matthis Synofzik, Raquel Sanchez-Valle, Fermin Moreno, Elizabeth Finger, Mario Masellis, Carmela Tartaglia, Rik Vandenberghe, Robert Laforce, Daniela Galimberti, Barbara Borroni, Chris R. Butler, Alexander Gerhard, Simon Ducharme, Jonathan D. Rohrer, Anna Månberg, Caroline Graff, Peter Nilsson, on behalf of the Genetic Frontotemporal Dementia Initiative (GENFI)
Formato:	article
Lenguaje:	EN
Publicado:	BMC 2021
Materias:	Cerebrospinal fluid Neurofilament medium polypeptide (NEFM) Neuronal pentraxin 2 (NPTX2) Neurosecretory protein VGF (VGF) Aquaporin 4 (AQP4) LASSO Neurology. Diseases of the nervous system RC346-429 Geriatrics RC952-954.6
Acceso en línea:	https://doaj.org/article/4c79ff7f1a074b35826ced4f2779339c
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spelling	oai:doaj.org-article:4c79ff7f1a074b35826ced4f2779339c2021-11-28T12:14:23ZA panel of CSF proteins separates genetic frontotemporal dementia from presymptomatic mutation carriers: a GENFI study10.1186/s13024-021-00499-41750-1326https://doaj.org/article/4c79ff7f1a074b35826ced4f2779339c2021-11-01T00:00:00Zhttps://doi.org/10.1186/s13024-021-00499-4https://doaj.org/toc/1750-1326Abstract Background A detailed understanding of the pathological processes involved in genetic frontotemporal dementia is critical in order to provide the patients with an optimal future treatment. Protein levels in CSF have the potential to reflect different pathophysiological processes in the brain. We aimed to identify and evaluate panels of CSF proteins with potential to separate symptomatic individuals from individuals without clinical symptoms (unaffected), as well as presymptomatic individuals from mutation non-carriers. Methods A multiplexed antibody-based suspension bead array was used to analyse levels of 111 proteins in CSF samples from 221 individuals from families with genetic frontotemporal dementia. The data was explored using LASSO and Random forest. Results When comparing affected individuals with unaffected individuals, 14 proteins were identified as potentially important for the separation. Among these, four were identified as most important, namely neurofilament medium polypeptide (NEFM), neuronal pentraxin 2 (NPTX2), neurosecretory protein VGF (VGF) and aquaporin 4 (AQP4). The combined profile of these four proteins successfully separated the two groups, with higher levels of NEFM and AQP4 and lower levels of NPTX2 in affected compared to unaffected individuals. VGF contributed to the models, but the levels were not significantly lower in affected individuals. Next, when comparing presymptomatic GRN and C9orf72 mutation carriers in proximity to symptom onset with mutation non-carriers, six proteins were identified with a potential to contribute to a separation, including progranulin (GRN). Conclusion In conclusion, we have identified several proteins with the combined potential to separate affected individuals from unaffected individuals, as well as proteins with potential to contribute to the separation between presymptomatic individuals and mutation non-carriers. Further studies are needed to continue the investigation of these proteins and their potential association to the pathophysiological mechanisms in genetic FTD.Sofia BergströmLinn ÖijerstedtJulia RemnestålJennie OlofssonAbbe UllgrenHarro SeelaarJohn C. van SwietenMatthis SynofzikRaquel Sanchez-ValleFermin MorenoElizabeth FingerMario MasellisCarmela TartagliaRik VandenbergheRobert LaforceDaniela GalimbertiBarbara BorroniChris R. ButlerAlexander GerhardSimon DucharmeJonathan D. RohrerAnna MånbergCaroline GraffPeter Nilssonon behalf of the Genetic Frontotemporal Dementia Initiative (GENFI)BMCarticleCerebrospinal fluidNeurofilament medium polypeptide (NEFM)Neuronal pentraxin 2 (NPTX2)Neurosecretory protein VGF (VGF)Aquaporin 4 (AQP4)LASSONeurology. Diseases of the nervous systemRC346-429GeriatricsRC952-954.6ENMolecular Neurodegeneration, Vol 16, Iss 1, Pp 1-14 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Cerebrospinal fluid Neurofilament medium polypeptide (NEFM) Neuronal pentraxin 2 (NPTX2) Neurosecretory protein VGF (VGF) Aquaporin 4 (AQP4) LASSO Neurology. Diseases of the nervous system RC346-429 Geriatrics RC952-954.6
spellingShingle	Cerebrospinal fluid Neurofilament medium polypeptide (NEFM) Neuronal pentraxin 2 (NPTX2) Neurosecretory protein VGF (VGF) Aquaporin 4 (AQP4) LASSO Neurology. Diseases of the nervous system RC346-429 Geriatrics RC952-954.6 Sofia Bergström Linn Öijerstedt Julia Remnestål Jennie Olofsson Abbe Ullgren Harro Seelaar John C. van Swieten Matthis Synofzik Raquel Sanchez-Valle Fermin Moreno Elizabeth Finger Mario Masellis Carmela Tartaglia Rik Vandenberghe Robert Laforce Daniela Galimberti Barbara Borroni Chris R. Butler Alexander Gerhard Simon Ducharme Jonathan D. Rohrer Anna Månberg Caroline Graff Peter Nilsson on behalf of the Genetic Frontotemporal Dementia Initiative (GENFI) A panel of CSF proteins separates genetic frontotemporal dementia from presymptomatic mutation carriers: a GENFI study
description	Abstract Background A detailed understanding of the pathological processes involved in genetic frontotemporal dementia is critical in order to provide the patients with an optimal future treatment. Protein levels in CSF have the potential to reflect different pathophysiological processes in the brain. We aimed to identify and evaluate panels of CSF proteins with potential to separate symptomatic individuals from individuals without clinical symptoms (unaffected), as well as presymptomatic individuals from mutation non-carriers. Methods A multiplexed antibody-based suspension bead array was used to analyse levels of 111 proteins in CSF samples from 221 individuals from families with genetic frontotemporal dementia. The data was explored using LASSO and Random forest. Results When comparing affected individuals with unaffected individuals, 14 proteins were identified as potentially important for the separation. Among these, four were identified as most important, namely neurofilament medium polypeptide (NEFM), neuronal pentraxin 2 (NPTX2), neurosecretory protein VGF (VGF) and aquaporin 4 (AQP4). The combined profile of these four proteins successfully separated the two groups, with higher levels of NEFM and AQP4 and lower levels of NPTX2 in affected compared to unaffected individuals. VGF contributed to the models, but the levels were not significantly lower in affected individuals. Next, when comparing presymptomatic GRN and C9orf72 mutation carriers in proximity to symptom onset with mutation non-carriers, six proteins were identified with a potential to contribute to a separation, including progranulin (GRN). Conclusion In conclusion, we have identified several proteins with the combined potential to separate affected individuals from unaffected individuals, as well as proteins with potential to contribute to the separation between presymptomatic individuals and mutation non-carriers. Further studies are needed to continue the investigation of these proteins and their potential association to the pathophysiological mechanisms in genetic FTD.
format	article
author	Sofia Bergström Linn Öijerstedt Julia Remnestål Jennie Olofsson Abbe Ullgren Harro Seelaar John C. van Swieten Matthis Synofzik Raquel Sanchez-Valle Fermin Moreno Elizabeth Finger Mario Masellis Carmela Tartaglia Rik Vandenberghe Robert Laforce Daniela Galimberti Barbara Borroni Chris R. Butler Alexander Gerhard Simon Ducharme Jonathan D. Rohrer Anna Månberg Caroline Graff Peter Nilsson on behalf of the Genetic Frontotemporal Dementia Initiative (GENFI)
author_facet	Sofia Bergström Linn Öijerstedt Julia Remnestål Jennie Olofsson Abbe Ullgren Harro Seelaar John C. van Swieten Matthis Synofzik Raquel Sanchez-Valle Fermin Moreno Elizabeth Finger Mario Masellis Carmela Tartaglia Rik Vandenberghe Robert Laforce Daniela Galimberti Barbara Borroni Chris R. Butler Alexander Gerhard Simon Ducharme Jonathan D. Rohrer Anna Månberg Caroline Graff Peter Nilsson on behalf of the Genetic Frontotemporal Dementia Initiative (GENFI)
author_sort	Sofia Bergström
title	A panel of CSF proteins separates genetic frontotemporal dementia from presymptomatic mutation carriers: a GENFI study
title_short	A panel of CSF proteins separates genetic frontotemporal dementia from presymptomatic mutation carriers: a GENFI study
title_full	A panel of CSF proteins separates genetic frontotemporal dementia from presymptomatic mutation carriers: a GENFI study
title_fullStr	A panel of CSF proteins separates genetic frontotemporal dementia from presymptomatic mutation carriers: a GENFI study
title_full_unstemmed	A panel of CSF proteins separates genetic frontotemporal dementia from presymptomatic mutation carriers: a GENFI study
title_sort	panel of csf proteins separates genetic frontotemporal dementia from presymptomatic mutation carriers: a genfi study
publisher	BMC
publishDate	2021
url	https://doaj.org/article/4c79ff7f1a074b35826ced4f2779339c
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A panel of CSF proteins separates genetic frontotemporal dementia from presymptomatic mutation carriers: a GENFI study

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