CSF glial markers are elevated in a subset of patients with genetic frontotemporal dementia
Neuroinflammation has been shown to be an important pathophysiological disease mechanism in frontotemporal dementia (FTD). This includes activation of microglia, a process that can be measured in life through assaying different glia-derived biomarkers in cerebrospinal fluid. However, only a few stud...
| Autores: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Tipo de recurso: | artículo |
| Estado: | Versión publicada |
| Fecha de publicación: | 2022 |
| País: | España |
| Institución: | Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya) |
| Repositorio: | Recercat. Dipósit de la Recerca de Catalunya |
| OAI Identifier: | oai:recercat.cat:2445/201467 |
| Acceso en línea: | https://hdl.handle.net/2445/201467 |
| Access Level: | acceso abierto |
| Palabra clave: | Marcadors bioquímics Demència Biochemical markers Dementia |
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CSF glial markers are elevated in a subset of patients with genetic frontotemporal dementia |
| title |
CSF glial markers are elevated in a subset of patients with genetic frontotemporal dementia |
| spellingShingle |
CSF glial markers are elevated in a subset of patients with genetic frontotemporal dementia Woollacott, Ione O. C. Marcadors bioquímics Demència Biochemical markers Dementia |
| title_short |
CSF glial markers are elevated in a subset of patients with genetic frontotemporal dementia |
| title_full |
CSF glial markers are elevated in a subset of patients with genetic frontotemporal dementia |
| title_fullStr |
CSF glial markers are elevated in a subset of patients with genetic frontotemporal dementia |
| title_full_unstemmed |
CSF glial markers are elevated in a subset of patients with genetic frontotemporal dementia |
| title_sort |
CSF glial markers are elevated in a subset of patients with genetic frontotemporal dementia |
| dc.creator.none.fl_str_mv |
Woollacott, Ione O. C. Swift, Imogen J. Sogorb Esteve, Aitana Heller, Carolin Knowles, Kathryn Bouzigues, Arabella Russell, Lucy L. Peakman, Georgia Greaves, Caroline V. Convery, Rhian Heslegrave, Amanda Rowe, James B. Borroni, Barbara Galimberti, Daniela Tiraboschi, Pietro Masellis, Mario Tartaglia, Maria Carmela Finger, Elizabeth Swieten, John C. van Seelaar, Harro Jiskoot, Lize Sorbi, Sandro Butler, Chris R. Graff, Caroline Gerhard, Alexander Laforce, Robert Sánchez Valle, Raquel Mendonça, Alexandre de Moreno, Fermin Synofzik, Matthis Vandenberghe, Rik Ducharme, Simon Le Ber, Isabelle Levin, Johannes Otto, Markus Pasquier, Florence Santana, Isabel Zetterberg, Henrik Rohrer, Jonathan D. |
| author |
Woollacott, Ione O. C. |
| author_facet |
Woollacott, Ione O. C. Swift, Imogen J. Sogorb Esteve, Aitana Heller, Carolin Knowles, Kathryn Bouzigues, Arabella Russell, Lucy L. Peakman, Georgia Greaves, Caroline V. Convery, Rhian Heslegrave, Amanda Rowe, James B. Borroni, Barbara Galimberti, Daniela Tiraboschi, Pietro Masellis, Mario Tartaglia, Maria Carmela Finger, Elizabeth Swieten, John C. van Seelaar, Harro Jiskoot, Lize Sorbi, Sandro Butler, Chris R. Graff, Caroline Gerhard, Alexander Laforce, Robert Sánchez Valle, Raquel Mendonça, Alexandre de Moreno, Fermin Synofzik, Matthis Vandenberghe, Rik Ducharme, Simon Le Ber, Isabelle Levin, Johannes Otto, Markus Pasquier, Florence Santana, Isabel Zetterberg, Henrik Rohrer, Jonathan D. |
| author_role |
author |
| author2 |
Swift, Imogen J. Sogorb Esteve, Aitana Heller, Carolin Knowles, Kathryn Bouzigues, Arabella Russell, Lucy L. Peakman, Georgia Greaves, Caroline V. Convery, Rhian Heslegrave, Amanda Rowe, James B. Borroni, Barbara Galimberti, Daniela Tiraboschi, Pietro Masellis, Mario Tartaglia, Maria Carmela Finger, Elizabeth Swieten, John C. van Seelaar, Harro Jiskoot, Lize Sorbi, Sandro Butler, Chris R. Graff, Caroline Gerhard, Alexander Laforce, Robert Sánchez Valle, Raquel Mendonça, Alexandre de Moreno, Fermin Synofzik, Matthis Vandenberghe, Rik Ducharme, Simon Le Ber, Isabelle Levin, Johannes Otto, Markus Pasquier, Florence Santana, Isabel Zetterberg, Henrik Rohrer, Jonathan D. |
| author2_role |
author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author |
| dc.subject.none.fl_str_mv |
Marcadors bioquímics Demència Biochemical markers Dementia |
| topic |
Marcadors bioquímics Demència Biochemical markers Dementia |
| description |
Neuroinflammation has been shown to be an important pathophysiological disease mechanism in frontotemporal dementia (FTD). This includes activation of microglia, a process that can be measured in life through assaying different glia-derived biomarkers in cerebrospinal fluid. However, only a few studies so far have taken place in FTD, and even fewer focusing on the genetic forms of FTD.We investigated the cerebrospinal fluid concentrations of TREM2, YKL-40 and chitotriosidase using immunoassays in 183 participants from the Genetic FTD Initiative (GENFI) study: 49 C9orf72 (36 presymptomatic, 13 symptomatic), 49 GRN (37 presymptomatic, 12 symptomatic) and 23 MAPT (16 presymptomatic, 7 symptomatic) mutation carriers and 62 mutation-negative controls. Concentrations were compared between groups using a linear regression model adjusting for age and sex, with 95% bias-corrected bootstrapped confidence intervals. Concentrations in each group were correlated with the Mini-Mental State Examination (MMSE) score using non-parametric partial correlations adjusting for age. Age-adjusted z-scores were also created for the concentration of markers in each participant, investigating how many had a value above the 95th percentile of controls.Only chitotriosidase in symptomatic GRN mutation carriers had a concentration significantly higher than controls. No group had higher TREM2 or YKL-40 concentrations than controls after adjusting for age and sex. There was a significant negative correlation of chitotriosidase concentration with MMSE in presymptomatic GRN mutation carriers. In the symptomatic groups, for TREM2 31% of C9orf72, 25% of GRN, and 14% of MAPT mutation carriers had a concentration above the 95th percentile of controls. For YKL-40 this was 8% C9orf72, 8% GRN and 0% MAPT mutation carriers, whilst for chitotriosidase it was 23% C9orf72, 50% GRN, and 29% MAPT mutation carriers.Although chitotriosidase concentrations in GRN mutation carriers were the only significantly raised glia-derived biomarker as a group, a subset of mutation carriers in all three groups, particularly for chitotriosidase and TREM2, had elevated concentrations. Further work is required to understand the variability in concentrations and the extent of neuroinflammation across the genetic forms of FTD. However, the current findings suggest limited utility of these measures in forthcoming trials.© 2022 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association. |
| publishDate |
2022 |
| dc.date.none.fl_str_mv |
2022 2023 2023 2023 |
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info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion |
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article |
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publishedVersion |
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https://hdl.handle.net/2445/201467 |
| url |
https://hdl.handle.net/2445/201467 |
| dc.language.none.fl_str_mv |
Inglés |
| language_invalid_str_mv |
Inglés |
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Reproducció del document publicat a: https://doi.org/10.1002/acn3.51672 Annals Of Clinical And Translational Neurology, 2022, vol. 9, num. 11, p. 1764-1777 https://doi.org/10.1002/acn3.51672 |
| dc.rights.none.fl_str_mv |
cc by (c) Woollacott, Ione O. C. et al., 2022 http://creativecommons.org/licenses/by/3.0/es/ info:eu-repo/semantics/openAccess |
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cc by (c) Woollacott, Ione O. C. et al., 2022 http://creativecommons.org/licenses/by/3.0/es/ |
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openAccess |
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14 p. application/pdf |
| dc.publisher.none.fl_str_mv |
Wiley |
| publisher.none.fl_str_mv |
Wiley |
| dc.source.none.fl_str_mv |
Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer) reponame:Recercat. Dipósit de la Recerca de Catalunya instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya) |
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Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya) |
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Recercat. Dipósit de la Recerca de Catalunya |
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Recercat. Dipósit de la Recerca de Catalunya |
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1869425025006698496 |
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CSF glial markers are elevated in a subset of patients with genetic frontotemporal dementiaWoollacott, Ione O. C.Swift, Imogen J.Sogorb Esteve, AitanaHeller, CarolinKnowles, KathrynBouzigues, ArabellaRussell, Lucy L.Peakman, GeorgiaGreaves, Caroline V.Convery, RhianHeslegrave, AmandaRowe, James B.Borroni, BarbaraGalimberti, DanielaTiraboschi, PietroMasellis, MarioTartaglia, Maria CarmelaFinger, ElizabethSwieten, John C. vanSeelaar, HarroJiskoot, LizeSorbi, SandroButler, Chris R.Graff, CarolineGerhard, AlexanderLaforce, RobertSánchez Valle, RaquelMendonça, Alexandre deMoreno, FerminSynofzik, MatthisVandenberghe, RikDucharme, SimonLe Ber, IsabelleLevin, JohannesOtto, MarkusPasquier, FlorenceSantana, IsabelZetterberg, HenrikRohrer, Jonathan D.Marcadors bioquímicsDemènciaBiochemical markersDementiaNeuroinflammation has been shown to be an important pathophysiological disease mechanism in frontotemporal dementia (FTD). This includes activation of microglia, a process that can be measured in life through assaying different glia-derived biomarkers in cerebrospinal fluid. However, only a few studies so far have taken place in FTD, and even fewer focusing on the genetic forms of FTD.We investigated the cerebrospinal fluid concentrations of TREM2, YKL-40 and chitotriosidase using immunoassays in 183 participants from the Genetic FTD Initiative (GENFI) study: 49 C9orf72 (36 presymptomatic, 13 symptomatic), 49 GRN (37 presymptomatic, 12 symptomatic) and 23 MAPT (16 presymptomatic, 7 symptomatic) mutation carriers and 62 mutation-negative controls. Concentrations were compared between groups using a linear regression model adjusting for age and sex, with 95% bias-corrected bootstrapped confidence intervals. Concentrations in each group were correlated with the Mini-Mental State Examination (MMSE) score using non-parametric partial correlations adjusting for age. Age-adjusted z-scores were also created for the concentration of markers in each participant, investigating how many had a value above the 95th percentile of controls.Only chitotriosidase in symptomatic GRN mutation carriers had a concentration significantly higher than controls. No group had higher TREM2 or YKL-40 concentrations than controls after adjusting for age and sex. There was a significant negative correlation of chitotriosidase concentration with MMSE in presymptomatic GRN mutation carriers. In the symptomatic groups, for TREM2 31% of C9orf72, 25% of GRN, and 14% of MAPT mutation carriers had a concentration above the 95th percentile of controls. For YKL-40 this was 8% C9orf72, 8% GRN and 0% MAPT mutation carriers, whilst for chitotriosidase it was 23% C9orf72, 50% GRN, and 29% MAPT mutation carriers.Although chitotriosidase concentrations in GRN mutation carriers were the only significantly raised glia-derived biomarker as a group, a subset of mutation carriers in all three groups, particularly for chitotriosidase and TREM2, had elevated concentrations. Further work is required to understand the variability in concentrations and the extent of neuroinflammation across the genetic forms of FTD. However, the current findings suggest limited utility of these measures in forthcoming trials.© 2022 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.Wiley2023202320222023info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersion14 p.application/pdfhttps://hdl.handle.net/2445/201467Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer)reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésReproducció del document publicat a: https://doi.org/10.1002/acn3.51672Annals Of Clinical And Translational Neurology, 2022, vol. 9, num. 11, p. 1764-1777https://doi.org/10.1002/acn3.51672cc by (c) Woollacott, Ione O. C. et al., 2022http://creativecommons.org/licenses/by/3.0/es/info:eu-repo/semantics/openAccessoai:recercat.cat:2445/2014672026-05-29T05:05:01Z |
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15,812429 |