Altered plasma protein profiles in genetic FTD – a GENFI study

Author:

Ullgren Abbe,Öijerstedt Linn,Olofsson Jennie,Bergström Sofia,Remnestål Julia,van Swieten John C.,Jiskoot Lize C.,Seelaar Harro,Borroni Barbara,Sanchez-Valle Raquel,Moreno Fermin,Laforce Robert,Synofzik Matthis,Galimberti Daniela,Rowe James B.,Masellis Mario,Tartaglia Maria Carmela,Finger Elizabeth,Vandenberghe Rik,de Mendonça Alexandre,Tirabosch Pietro,Santana Isabel,Ducharme Simon,Butler Chris R.,Gerhard Alexander,Otto Markus,Bouzigues Arabella,Russell Lucy,Swift Imogen J.,Sogorb-Esteve Aitana,Heller Carolin,Rohrer Jonathan D.,Månberg Anna,Nilsson Peter,Graff CarolineORCID,Afonso Sónia,Almeida Maria Rosario,Anderl-Straub Sarah,Andersson Christin,Antonell Anna,Arighi Andrea,Balasa Mircea,Barandiaran Myriam,Bargalló Nuria,Bartha Robart,Bender Benjamin,Buratti Emanuele,Benussi Luisa,Bertoux Maxime,Binetti Giuliano,Black Sandra,Bocchetta Martina,Borrego-Ecija Sergi,Bras Jose,Bruffaerts Rose,Cañada Marta,Cantoni Valentina,Caroppo Paola,Cash David,Castelo-Branco Miguel,Convery Rhian,Cope Thomas,Deramecourt Vincent,Di Fede Giuseppe,Díez Alina,Fenoglio Chiara,Ferreira Catarina B.,Fox Nick,Freedman Morris,Fumagalli Giorgio,Funkiewiez Aurélie,Gabilondo Alazne,Gasparotti Roberto,Gauthier Serge,Alberici Antonella,Giaccone Giorgio,Gorostidi Ana,Greaves Caroline,Guerreiro Rita,Indakoetxea Begoña,Jelic Vesna,Karnath Hans-Otto,Keren Ron,Kuchcinski Gregory,Langheinrich Tobias,Lebouvier Thibaud,Leitão Maria João,Lladó Albert,Maruta Carolina,Meeter Lieke,Miltenberger Gabriel,van Minkelen Rick,Mitchell Sara,Moore Katrina,Nicholas Jennifer,Olives Jaume,Ourselin Sebastien,Padovani Alessandro,Panman Jessica,Papma Janne M.,Peakman Georgia,Pievani Michela,Pijnenburg Yolande,Premi Enrico,Prioni Sara,Rademakers Rosa,Redaelli Veronica,Rinaldi Daisy,Rittman Tim,Rogaeva Ekaterina,Rollin Adeline,Rosa-Neto Pedro,Rossi Giacomina,Rosser Martin,Scarpini Elio,Semler Elisa,Shafei Rachelle,Shoesmith Christen,Tábuas-Pereira Miguel,Tainta Mikel,Taipa Ricardo,Tang-Wai David,Thomas David L.,Thompson Paul,Thonberg Håkan,Timberlake Carolyn,Todd Emily,Van Damme Philip,Vandenbulcke Mathieu,Veldsman Michele,Verdelho Ana,Villanua Jorge,Warren Jason,Wilke Carlo,Woollacott Ione,Zetterberg Henrik,Zulaica Miren,Durães João,Lima Marisa,Lemos João,

Abstract

Abstract Background Plasma biomarkers reflecting the pathology of frontotemporal dementia would add significant value to clinical practice, to the design and implementation of treatment trials as well as our understanding of disease mechanisms. The aim of this study was to explore the levels of multiple plasma proteins in individuals from families with genetic frontotemporal dementia. Methods Blood samples from 693 participants in the GENetic Frontotemporal Dementia Initiative study were analysed using a multiplexed antibody array targeting 158 proteins. Results We found 13 elevated proteins in symptomatic mutation carriers, when comparing plasma levels from people diagnosed with genetic FTD to healthy non-mutation controls and 10 proteins that were elevated compared to presymptomatic mutation carriers. Conclusion We identified plasma proteins with altered levels in symptomatic mutation carriers compared to non-carrier controls as well as to presymptomatic mutation carriers. Further investigations are needed to elucidate their potential as fluid biomarkers of the disease process.

Funder

Schörling Foundation

Vetenskapsrådet

Diorapthe Foundation

the Association for Frontotemporal Dementias

The Netherlands Organization for Scientific Research

ZonMw Memorabel

JPND, Ministero della Salute

Familjen Erling-Perssons Stiftelse

Alzheimerfonden

Hjärnfonden

Demensfonden

Åhlén-stiftelsen

Region Stockholm

Medical Research Center Clinician Scientist Fellowship

Miriam Marks Brain Research UK Sr Fellowship

University College London Hospitals Biomedical Research Centre

NIHR Rare Disease Translational Research Collaboration

Medical Research Council

ZonMw

Bundesministerium für Bildung und Forschung

Ministero dell’Istruzione, dell’Università e della Ricerca

Canadian Institute of Health Research

Tau Consortium

the Welcome Trust

NIHR Cambridge Biomedical Research Centre

Weston Brain Institute

Ontario Brain Institute

Alzheimer’s Research UK

Fundació la Marató de TV3

Mady Browaeys Fund for Research into Frontotemporal Dementia

The Bluefield Project

Karolinska Institute

Publisher

Springer Science and Business Media LLC

Subject

Cellular and Molecular Neuroscience,Neurology (clinical),Molecular Biology

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