Altered plasma protein profiles in genetic FTD – a GENFI study
Authors: 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 Caroline ,   on behalf of the Genetic Frontotemporal Dementia Initiative (GENFI), 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 
Published: November 2023

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.