CSF glial markers are elevated in a subset of patients with genetic frontotemporal dementia
| Autor(a) principal: | |
|---|---|
| Data de Publicação: | 2022 |
| Outros Autores: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
| Tipo de documento: | Artigo |
| Idioma: | eng |
| Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
| Texto Completo: | http://hdl.handle.net/10451/54838 |
Resumo: | © 2022 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
| id |
RCAP_535d1370796e65d1d32f32ea645588fd |
|---|---|
| oai_identifier_str |
oai:repositorio.ul.pt:10451/54838 |
| network_acronym_str |
RCAP |
| network_name_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
| repository_id_str |
7160 |
| spelling |
CSF glial markers are elevated in a subset of patients with genetic frontotemporal dementia© 2022 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.Background: 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. Methods: 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. Results: 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. Conclusions: 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.The Dementia Research Centre is supported by Alzheimer's Research UK, Alzheimer's Society, Brain Research UK, and The Wolfson Foundation. This work was supported by the NIHR UCL/H Biomedical Research Centre, the Leonard Wolfson Experimental Neurology Centre (LWENC) Clinical Research Facility, and the UK Dementia Research Institute, which receives its funding from UK DRI Ltd, funded by the UK Medical Research Council, Alzheimer's Society and Alzheimer's Research UK. IOCW was supported by an MRC Clinical Research Training Fellowship (MR/M018288/1). JDR is supported by the Miriam Marks Brain Research UK Senior Fellowship and has received funding from an MRC Clinician Scientist Fellowship (MR/M008525/1) and the NIHR Rare Disease Translational Research Collaboration (BRC149/NS/MH). This work was also supported by the MRC UK GENFI grant (MR/M023664/1), the Bluefield Project and the JPND GENFI-PROX grant (2019-02248). Several authors of this publication are members of the European Reference Network for Rare Neurological Diseases – Project ID No 739510. RC/CG are supported by a Frontotemporal Dementia Research Studentships in Memory of David Blechner funded through The National Brain Appeal (RCN 290173). MB is supported by a Fellowship award from the Alzheimer's Society, UK (AS-JF-19a-004-517). MB's work is also supported by the UK Dementia Research Institute which receives its funding from DRI Ltd, funded by the UK Medical Research Council, Alzheimer's Society and Alzheimer's Research UK. JCVS was supported by the Dioraphte Foundation grant 09-02-03-00, the Association for Frontotemporal Dementias Research Grant 2009, The Netherlands Organisation for Scientific Research (NWO) grant HCMI 056-13-018, ZonMw Memorabel (Deltaplan Dementie, project number 733 051 042), Alzheimer Nederland and the Bluefield project. FM received funding from the Tau Consortium and the Center for Networked Biomedical Research on Neurodegenerative Disease (CIBERNED). RS-V has received funding from Fundació Marató de TV3, Spain (grant no. 20143810). CG received funding from JPND-Prefrontals VR Dnr 529-2014-7504, VR 2015-02926 and 2018-02754, the Swedish FTD Inititative-Schörling Foundation, Alzheimer Foundation, Brain Foundation and Stockholm County Council ALF. MM has received funding from a Canadian Institute of Health Research operating grant and the Weston Brain Institute and Ontario Brain Institute. JBR has received funding from the Welcome Trust (220258), the Cambridge University Centre for Frontotemporal Dementia, the Medical Research Council (SUAG/051 G101400) and the National Institute for Health Research (NIHR) Cambridge Biomedical Research Centre (BRC-1215-20014). EF has received funding from a CIHR grant #327387. DG received support from the EU Joint Programme – Neurodegenerative Disease Research (JPND) and the Italian Ministry of Health (PreFrontALS) grant 733051042. RV has received funding from the Mady Browaeys Fund for Research into Frontotemporal Dementia. MO has received funding from BMBF (FTLDc). HZ is a Wallenberg Scholar supported by grants from the Swedish Research Council (#2018-02532), the European Research Council (#681712), Swedish State Support for Clinical Research (#ALFGBG-720931), the Alzheimer Drug Discovery Foundation (ADDF), USA (#201809-2016862), the AD Strategic Fund and the Alzheimer's Association (#ADSF-21-831376-C, #ADSF-21-831381-C and #ADSF-21-831377-C), the Olav Thon Foundation, the Erling-Persson Family Foundation, Stiftelsen för Gamla Tjänarinnor, Hjärnfonden, Sweden (#FO2019-0228), the European Union's Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No 860197 (MIRIADE), European Union Joint Program for Neurodegenerative Disorders (JPND2021-00694), and the UK Dementia Research Institute at UCL. JL received funding for this work by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany's Excellence Strategy within the framework of the Munich Cluster for Systems Neurology (EXC 2145 SyNergy – ID 390857198).WileyRepositório da Universidade de LisboaWoollacott, 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, Elizabethvan Swieten, John C.Seelaar, HarroJiskoot, LizeSorbi, SandroButler, Chris R.Graff, CarolineGerhard, AlexanderLaforce, RobertSanchez‐Valle, RaquelDe Mendonça, AlexandreMoreno, FerminSynofzik, MatthisVandenberghe, RikDucharme, SimonBer, Isabelle LeLevin, JohannesOtto, MarkusPasquier, FlorenceSantana, IsabelZetterberg, HenrikRohrer, Jonathan D.2022-10-20T14:36:01Z20222022-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10451/54838engAnn Clin Transl Neurol. 2022 Oct 1710.1002/acn3.516722328-9503info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-11-08T17:01:28Zoai:repositorio.ul.pt:10451/54838Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T22:05:35.771763Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
| dc.title.none.fl_str_mv |
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. |
| 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 |
| 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 van Swieten, John C. Seelaar, Harro Jiskoot, Lize Sorbi, Sandro Butler, Chris R. Graff, Caroline Gerhard, Alexander Laforce, Robert Sanchez‐Valle, Raquel De Mendonça, Alexandre Moreno, Fermin Synofzik, Matthis Vandenberghe, Rik Ducharme, Simon Ber, Isabelle Le 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 van Swieten, John C. Seelaar, Harro Jiskoot, Lize Sorbi, Sandro Butler, Chris R. Graff, Caroline Gerhard, Alexander Laforce, Robert Sanchez‐Valle, Raquel De Mendonça, Alexandre Moreno, Fermin Synofzik, Matthis Vandenberghe, Rik Ducharme, Simon Ber, Isabelle Le 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.contributor.none.fl_str_mv |
Repositório da Universidade de Lisboa |
| dc.contributor.author.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 van Swieten, John C. Seelaar, Harro Jiskoot, Lize Sorbi, Sandro Butler, Chris R. Graff, Caroline Gerhard, Alexander Laforce, Robert Sanchez‐Valle, Raquel De Mendonça, Alexandre Moreno, Fermin Synofzik, Matthis Vandenberghe, Rik Ducharme, Simon Ber, Isabelle Le Levin, Johannes Otto, Markus Pasquier, Florence Santana, Isabel Zetterberg, Henrik Rohrer, Jonathan D. |
| description |
© 2022 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
| publishDate |
2022 |
| dc.date.none.fl_str_mv |
2022-10-20T14:36:01Z 2022 2022-01-01T00:00:00Z |
| dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
| dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
| format |
article |
| status_str |
publishedVersion |
| dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10451/54838 |
| url |
http://hdl.handle.net/10451/54838 |
| dc.language.iso.fl_str_mv |
eng |
| language |
eng |
| dc.relation.none.fl_str_mv |
Ann Clin Transl Neurol. 2022 Oct 17 10.1002/acn3.51672 2328-9503 |
| dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
| eu_rights_str_mv |
openAccess |
| dc.format.none.fl_str_mv |
application/pdf |
| dc.publisher.none.fl_str_mv |
Wiley |
| publisher.none.fl_str_mv |
Wiley |
| dc.source.none.fl_str_mv |
reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
| instname_str |
Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
| instacron_str |
RCAAP |
| institution |
RCAAP |
| reponame_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
| collection |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
| repository.name.fl_str_mv |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
| repository.mail.fl_str_mv |
|
| _version_ |
1799134608135028736 |