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

Bergstrom, S; Oijerstedt, L; Remnestal, J; Olofsson, J; Ullgren, A; Seelaar, H; van Swieten, JC; ... Nilsson, P; + view all (2021) A panel of CSF proteins separates genetic frontotemporal dementia from presymptomatic mutation carriers: a GENFI study. Molecular Neurodegeneration , 16 (1) , Article 79. 10.1186/s13024-021-00499-4. Green open access

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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.

Type: Article
Title: A panel of CSF proteins separates genetic frontotemporal dementia from presymptomatic mutation carriers: a GENFI study
Open access status: An open access version is available from UCL Discovery
DOI: 10.1186/s13024-021-00499-4
Publisher version: https://doi.org/10.1186/s13024-021-00499-4
Language: English
Additional information: This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third-party material in this article are included in the Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
Keywords: Science & Technology, Life Sciences & Biomedicine, Neurosciences, Neurosciences & Neurology, Cerebrospinal fluid, Neurofilament medium polypeptide (NEFM), Neuronal pentraxin 2 (NPTX2), Neurosecretory protein VGF (VGF), Aquaporin 4 (AQP4), LASSO, Random forest, Suspension bead array, CEREBROSPINAL-FLUID, CRITERIA, DISEASE
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Neurodegenerative Diseases
URI: https://discovery.ucl.ac.uk/id/eprint/10142443
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