Stratifying the presymptomatic phase of genetic frontotemporal dementia by Serum NfL and pNfH: a longitudinal multicentre study
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Data de Publicação: | 2021 |
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/10451/50716 |
Resumo: | © 2021 The Authors. Annals of 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. |
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Stratifying the presymptomatic phase of genetic frontotemporal dementia by Serum NfL and pNfH: a longitudinal multicentre study© 2021 The Authors. Annals of 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.Objective: Although the presymptomatic stages of frontotemporal dementia (FTD) provide a unique chance to delay or even prevent neurodegeneration by early intervention, they remain poorly defined. Leveraging a large multicenter cohort of genetic FTD mutation carriers, we provide a biomarker-based stratification and biomarker cascade of the likely most treatment-relevant stage within the presymptomatic phase: the conversion stage. Methods: We longitudinally assessed serum levels of neurofilament light (NfL) and phosphorylated neurofilament heavy (pNfH) in the Genetic FTD Initiative (GENFI) cohort (n = 444), using single-molecule array technique. Subjects comprised 91 symptomatic and 179 presymptomatic subjects with mutations in the FTD genes C9orf72, GRN, or MAPT, and 174 mutation-negative within-family controls. Results: In a biomarker cascade, NfL increase preceded the hypothetical clinical onset by 15 years and concurred with brain atrophy onset, whereas pNfH increase started close to clinical onset. The conversion stage was marked by increased NfL, but still normal pNfH levels, while both were increased at the symptomatic stage. Intra-individual change rates were increased for NfL at the conversion stage and for pNfH at the symptomatic stage, highlighting their respective potential as stage-dependent dynamic biomarkers within the biomarker cascade. Increased NfL levels and NfL change rates allowed identification of presymptomatic subjects converting to symptomatic disease and capture of proximity-to-onset. We estimate stage-dependent sample sizes for trials aiming to decrease neurofilament levels or change rates. Interpretation: Blood NfL and pNfH provide dynamic stage-dependent stratification and, potentially, treatment response biomarkers in presymptomatic FTD, allowing demarcation of the conversion stage. The proposed biomarker cascade might pave the way towards a biomarker-based precision medicine approach to genetic FTD..W. and M.S. are members of the European Reference Network for Rare Neurological Diseases Project ID No. 739510. This work was supported by the Horizon 2020 research and innovation program (grant 779257 Solve-RD to M.S.), the National Ataxia Foundation (grant to C.W. and M.S.), the Wilhelm Vaillant Stiftung (grant to C.W.), the EU Joint Programme – Neurodegenerative Disease Research (JPND) “GENFI-prox” through participating national funding agencies (by DLR/BMBF to M.S., J.D.R., B.B., C.G., and M.O.), and the European Union's Horizon 2020 research and innovation programme under grant agreement No. 643417. J.C.S. and H.S. received funding by two Memorabel grants from Deltaplan Dementie (The Netherlands Organisation for Health Research and Development and Alzheimer Nederland; grant numbers 733050813 and 733050103) in the Netherlands and the Bluefield Project to Cure Frontotemporal Dementia. J.B.R. was supported by the NIHR Cambridge Biomedical Research Centre (BRC-1215-20014) and the Medical Research Council (SUAG/051 G101400). C.B. is supported by a postdoctoral fellowship from the Swiss National Science Foundation (P400PM_191077). J.D.R. 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).WileyRepositório da Universidade de LisboaWilke, CarloReich, SelinaSwieten, John C.Borroni, BarbaraSanchez‐Valle, RaquelMoreno, FerminLaforce, RobertGraff, CarolineGalimberti, DanielaRowe, James B.Masellis, MarioTartaglia, Maria C.Finger, ElizabethVandenberghe, RikDe Mendonça, AlexandreTagliavini, FabrizioSantana, IsabelDucharme, SimonButler, Chris R.Gerhard, AlexanderLevin, JohannesDanek, AdrianOtto, MarkusFrisoni, GiovanniGhidoni, RobertaSorbi, SandroBocchetta, MartinaTodd, EmilyKuhle, JensBarro, ChristianAfonso, SóniaAlmeida, Maria RosarioAnderl‐Straub, SarahAndersson, ChristinAntonell, AnnaArchetti, SilvanaArighi, AndreaBalasa, MirceaBarandiaran, MyriamBargalló, NuriaBartha, RobartBender, BenjaminBenussi, AlbertoBenussi, LuisaBessi, ValentinaBinetti, GiulianoBlack, SandraBorrego‐Ecija, SergiBras, JoseBruffaerts, RoseCañada, MartaCantoni, ValentinaCaroppo, PaolaCash, DavidCastelo-Branco, MiguelConvery, RhianCope, ThomasDi Fede, GiuseppeDíez, AlinaDuro, DianaFenoglio, ChiaraFerrari, CamillaFerreira, Catarina B.Fox, NickFreedman, MorrisFumagalli, GiorgioGabilondo, AlazneGasparotti, RobertoGauthier, SergeGazzina, StefanoGiaccone, GiorgioGorostidi, AnaGreaves, CarolineGuerreiro, RitaHeller, CarolinHoegen, TobiasIndakoetxea, BegoñaJelic, VesnaJiskoot, LizeKarnath, Hans‐OttoKeren, RonLangheinrich, TobiasLeitão, Maria JoãoLladó, AlbertLombardi, GemmaLoosli, SandraMaruta, CarolinaMead, SimonMeeter, LiekeMiltenberger-Miltenyi, GabrielMinkelen, RickMitchell, SaraMoore, KatrinaNacmias, BenedettaNicholas, JenniferÖijerstedt, LinnOlives, JaumeOurselin, SebastienPadovani, AlessandroPanman, JessicaPapma, Janne M.Peakman, GeorgiaPievani, MichelaPijnenburg, YolandePolito, CristinaPremi, EnricoPrioni, SaraPrix, CatharinaRademakers, RosaRedaelli, VeronicaRittman, TimRogaeva, EkaterinaRosa‐Neto, PedroRossi, GiacominaRosser, MartinSantiago, BeatrizScarpini, ElioSchönecker, SonjaSeelaar, HarroSemler, ElisaShafei, RachelleShoesmith, ChristenTábuas‐Pereira, MiguelTainta, MikelTaipa, RicardoTang‐Wai, DavidThomas, David L.Thompson, PaulThonberg, HakanTimberlake, CarolynTiraboschi, PietroVan Damme, PhilipVandenbulcke, MathieuVeldsman, MicheleVerdelho, AnaVillanua, JorgeWarren, JasonWoollacott, IoneWlasich, ElisabethZetterberg, HenrikZulaica, MirenRohrer, Jonathan D.Synofzik, Matthis2022-01-05T16:49:20Z20212021-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10451/50716engAnn Neurol. 2022 Jan;91(1):33-470364-513410.1002/ana.262651531-8249info: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:RCAAP2023-11-08T16:55:02Zoai:repositorio.ul.pt:10451/50716Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T22:02:07.203345Repositório 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 |
Stratifying the presymptomatic phase of genetic frontotemporal dementia by Serum NfL and pNfH: a longitudinal multicentre study |
title |
Stratifying the presymptomatic phase of genetic frontotemporal dementia by Serum NfL and pNfH: a longitudinal multicentre study |
spellingShingle |
Stratifying the presymptomatic phase of genetic frontotemporal dementia by Serum NfL and pNfH: a longitudinal multicentre study Wilke, Carlo |
title_short |
Stratifying the presymptomatic phase of genetic frontotemporal dementia by Serum NfL and pNfH: a longitudinal multicentre study |
title_full |
Stratifying the presymptomatic phase of genetic frontotemporal dementia by Serum NfL and pNfH: a longitudinal multicentre study |
title_fullStr |
Stratifying the presymptomatic phase of genetic frontotemporal dementia by Serum NfL and pNfH: a longitudinal multicentre study |
title_full_unstemmed |
Stratifying the presymptomatic phase of genetic frontotemporal dementia by Serum NfL and pNfH: a longitudinal multicentre study |
title_sort |
Stratifying the presymptomatic phase of genetic frontotemporal dementia by Serum NfL and pNfH: a longitudinal multicentre study |
author |
Wilke, Carlo |
author_facet |
Wilke, Carlo Reich, Selina Swieten, John C. Borroni, Barbara Sanchez‐Valle, Raquel Moreno, Fermin Laforce, Robert Graff, Caroline Galimberti, Daniela Rowe, James B. Masellis, Mario Tartaglia, Maria C. Finger, Elizabeth Vandenberghe, Rik De Mendonça, Alexandre Tagliavini, Fabrizio Santana, Isabel Ducharme, Simon Butler, Chris R. Gerhard, Alexander Levin, Johannes Danek, Adrian Otto, Markus Frisoni, Giovanni Ghidoni, Roberta Sorbi, Sandro Bocchetta, Martina Todd, Emily Kuhle, Jens Barro, Christian Afonso, Sónia Almeida, Maria Rosario Anderl‐Straub, Sarah Andersson, Christin Antonell, Anna Archetti, Silvana Arighi, Andrea Balasa, Mircea Barandiaran, Myriam Bargalló, Nuria Bartha, Robart Bender, Benjamin Benussi, Alberto Benussi, Luisa Bessi, Valentina Binetti, Giuliano Black, Sandra Borrego‐Ecija, Sergi Bras, Jose Bruffaerts, Rose Cañada, Marta Cantoni, Valentina Caroppo, Paola Cash, David Castelo-Branco, Miguel Convery, Rhian Cope, Thomas Di Fede, Giuseppe Díez, Alina Duro, Diana Fenoglio, Chiara Ferrari, Camilla Ferreira, Catarina B. Fox, Nick Freedman, Morris Fumagalli, Giorgio Gabilondo, Alazne Gasparotti, Roberto Gauthier, Serge Gazzina, Stefano Giaccone, Giorgio Gorostidi, Ana Greaves, Caroline Guerreiro, Rita Heller, Carolin Hoegen, Tobias Indakoetxea, Begoña Jelic, Vesna Jiskoot, Lize Karnath, Hans‐Otto Keren, Ron Langheinrich, Tobias Leitão, Maria João Lladó, Albert Lombardi, Gemma Loosli, Sandra Maruta, Carolina Mead, Simon Meeter, Lieke Miltenberger-Miltenyi, Gabriel Minkelen, Rick Mitchell, Sara Moore, Katrina Nacmias, Benedetta Nicholas, Jennifer Öijerstedt, Linn Olives, Jaume Ourselin, Sebastien Padovani, Alessandro Panman, Jessica Papma, Janne M. Peakman, Georgia Pievani, Michela Pijnenburg, Yolande Polito, Cristina Premi, Enrico Prioni, Sara Prix, Catharina Rademakers, Rosa Redaelli, Veronica Rittman, Tim Rogaeva, Ekaterina Rosa‐Neto, Pedro Rossi, Giacomina Rosser, Martin Santiago, Beatriz Scarpini, Elio Schönecker, Sonja Seelaar, Harro Semler, Elisa Shafei, Rachelle Shoesmith, Christen Tábuas‐Pereira, Miguel Tainta, Mikel Taipa, Ricardo Tang‐Wai, David Thomas, David L. Thompson, Paul Thonberg, Hakan Timberlake, Carolyn Tiraboschi, Pietro Van Damme, Philip Vandenbulcke, Mathieu Veldsman, Michele Verdelho, Ana Villanua, Jorge Warren, Jason Woollacott, Ione Wlasich, Elisabeth Zetterberg, Henrik Zulaica, Miren Rohrer, Jonathan D. Synofzik, Matthis |
author_role |
author |
author2 |
Reich, Selina Swieten, John C. Borroni, Barbara Sanchez‐Valle, Raquel Moreno, Fermin Laforce, Robert Graff, Caroline Galimberti, Daniela Rowe, James B. Masellis, Mario Tartaglia, Maria C. Finger, Elizabeth Vandenberghe, Rik De Mendonça, Alexandre Tagliavini, Fabrizio Santana, Isabel Ducharme, Simon Butler, Chris R. Gerhard, Alexander Levin, Johannes Danek, Adrian Otto, Markus Frisoni, Giovanni Ghidoni, Roberta Sorbi, Sandro Bocchetta, Martina Todd, Emily Kuhle, Jens Barro, Christian Afonso, Sónia Almeida, Maria Rosario Anderl‐Straub, Sarah Andersson, Christin Antonell, Anna Archetti, Silvana Arighi, Andrea Balasa, Mircea Barandiaran, Myriam Bargalló, Nuria Bartha, Robart Bender, Benjamin Benussi, Alberto Benussi, Luisa Bessi, Valentina Binetti, Giuliano Black, Sandra Borrego‐Ecija, Sergi Bras, Jose Bruffaerts, Rose Cañada, Marta Cantoni, Valentina Caroppo, Paola Cash, David Castelo-Branco, Miguel Convery, Rhian Cope, Thomas Di Fede, Giuseppe Díez, Alina Duro, Diana Fenoglio, Chiara Ferrari, Camilla Ferreira, Catarina B. Fox, Nick Freedman, Morris Fumagalli, Giorgio Gabilondo, Alazne Gasparotti, Roberto Gauthier, Serge Gazzina, Stefano Giaccone, Giorgio Gorostidi, Ana Greaves, Caroline Guerreiro, Rita Heller, Carolin Hoegen, Tobias Indakoetxea, Begoña Jelic, Vesna Jiskoot, Lize Karnath, Hans‐Otto Keren, Ron Langheinrich, Tobias Leitão, Maria João Lladó, Albert Lombardi, Gemma Loosli, Sandra Maruta, Carolina Mead, Simon Meeter, Lieke Miltenberger-Miltenyi, Gabriel Minkelen, Rick Mitchell, Sara Moore, Katrina Nacmias, Benedetta Nicholas, Jennifer Öijerstedt, Linn Olives, Jaume Ourselin, Sebastien Padovani, Alessandro Panman, Jessica Papma, Janne M. Peakman, Georgia Pievani, Michela Pijnenburg, Yolande Polito, Cristina Premi, Enrico Prioni, Sara Prix, Catharina Rademakers, Rosa Redaelli, Veronica Rittman, Tim Rogaeva, Ekaterina Rosa‐Neto, Pedro Rossi, Giacomina Rosser, Martin Santiago, Beatriz Scarpini, Elio Schönecker, Sonja Seelaar, Harro Semler, Elisa Shafei, Rachelle Shoesmith, Christen Tábuas‐Pereira, Miguel Tainta, Mikel Taipa, Ricardo Tang‐Wai, David Thomas, David L. Thompson, Paul Thonberg, Hakan Timberlake, Carolyn Tiraboschi, Pietro Van Damme, Philip Vandenbulcke, Mathieu Veldsman, Michele Verdelho, Ana Villanua, Jorge Warren, Jason Woollacott, Ione Wlasich, Elisabeth Zetterberg, Henrik Zulaica, Miren Rohrer, Jonathan D. Synofzik, Matthis |
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 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 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 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 |
Wilke, Carlo Reich, Selina Swieten, John C. Borroni, Barbara Sanchez‐Valle, Raquel Moreno, Fermin Laforce, Robert Graff, Caroline Galimberti, Daniela Rowe, James B. Masellis, Mario Tartaglia, Maria C. Finger, Elizabeth Vandenberghe, Rik De Mendonça, Alexandre Tagliavini, Fabrizio Santana, Isabel Ducharme, Simon Butler, Chris R. Gerhard, Alexander Levin, Johannes Danek, Adrian Otto, Markus Frisoni, Giovanni Ghidoni, Roberta Sorbi, Sandro Bocchetta, Martina Todd, Emily Kuhle, Jens Barro, Christian Afonso, Sónia Almeida, Maria Rosario Anderl‐Straub, Sarah Andersson, Christin Antonell, Anna Archetti, Silvana Arighi, Andrea Balasa, Mircea Barandiaran, Myriam Bargalló, Nuria Bartha, Robart Bender, Benjamin Benussi, Alberto Benussi, Luisa Bessi, Valentina Binetti, Giuliano Black, Sandra Borrego‐Ecija, Sergi Bras, Jose Bruffaerts, Rose Cañada, Marta Cantoni, Valentina Caroppo, Paola Cash, David Castelo-Branco, Miguel Convery, Rhian Cope, Thomas Di Fede, Giuseppe Díez, Alina Duro, Diana Fenoglio, Chiara Ferrari, Camilla Ferreira, Catarina B. Fox, Nick Freedman, Morris Fumagalli, Giorgio Gabilondo, Alazne Gasparotti, Roberto Gauthier, Serge Gazzina, Stefano Giaccone, Giorgio Gorostidi, Ana Greaves, Caroline Guerreiro, Rita Heller, Carolin Hoegen, Tobias Indakoetxea, Begoña Jelic, Vesna Jiskoot, Lize Karnath, Hans‐Otto Keren, Ron Langheinrich, Tobias Leitão, Maria João Lladó, Albert Lombardi, Gemma Loosli, Sandra Maruta, Carolina Mead, Simon Meeter, Lieke Miltenberger-Miltenyi, Gabriel Minkelen, Rick Mitchell, Sara Moore, Katrina Nacmias, Benedetta Nicholas, Jennifer Öijerstedt, Linn Olives, Jaume Ourselin, Sebastien Padovani, Alessandro Panman, Jessica Papma, Janne M. Peakman, Georgia Pievani, Michela Pijnenburg, Yolande Polito, Cristina Premi, Enrico Prioni, Sara Prix, Catharina Rademakers, Rosa Redaelli, Veronica Rittman, Tim Rogaeva, Ekaterina Rosa‐Neto, Pedro Rossi, Giacomina Rosser, Martin Santiago, Beatriz Scarpini, Elio Schönecker, Sonja Seelaar, Harro Semler, Elisa Shafei, Rachelle Shoesmith, Christen Tábuas‐Pereira, Miguel Tainta, Mikel Taipa, Ricardo Tang‐Wai, David Thomas, David L. Thompson, Paul Thonberg, Hakan Timberlake, Carolyn Tiraboschi, Pietro Van Damme, Philip Vandenbulcke, Mathieu Veldsman, Michele Verdelho, Ana Villanua, Jorge Warren, Jason Woollacott, Ione Wlasich, Elisabeth Zetterberg, Henrik Zulaica, Miren Rohrer, Jonathan D. Synofzik, Matthis |
description |
© 2021 The Authors. Annals of 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 |
2021 |
dc.date.none.fl_str_mv |
2021 2021-01-01T00:00:00Z 2022-01-05T16:49:20Z |
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/10451/50716 |
url |
http://hdl.handle.net/10451/50716 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Ann Neurol. 2022 Jan;91(1):33-47 0364-5134 10.1002/ana.26265 1531-8249 |
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info:eu-repo/semantics/openAccess |
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openAccess |
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application/pdf |
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Wiley |
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Wiley |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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