CSF glial markers are elevated in a subset of patients with genetic frontotemporal dementia. Issue 11 (17th October 2022)

• Record Type: Journal Article
• Authors: 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.;
• Other Names: Nelson Annabel investigator.; Bocchetta Martina investigator.; Cash David investigator.; Thomas David L. investigator.; Todd Emily investigator.; Benotmane Hanya investigator.; Nicholas Jennifer investigator.; Samra Kiran investigator.; Shafei Rachelle investigator.; Timberlake Carolyn investigator.; Cope Thomas investigator.; Rittman Timothy investigator.; Benussi Alberto investigator.; Premi Enrico investigator.; Gasparotti Roberto investigator.; Archetti Silvana investigator.; Gazzina Stefano investigator.; Cantoni Valentina investigator.; Arighi Andrea investigator.; Fenoglio Chiara investigator.; Scarpini Elio investigator.; Fumagalli Giorgio investigator.; Borracci Vittoria investigator.; Rossi Giacomina investigator.; Giaccone Giorgio investigator.; Di Fede Giuseppe investigator.; Caroppo Paola investigator.; Prioni Sara investigator.; Redaelli Veronica investigator.; Tang‐Wai David investigator.; Rogaeva Ekaterina investigator.; Castelo‐Branco Miguel investigator.; Freedman Morris investigator.; Keren Ron investigator.; Black Sandra investigator.; Mitchell Sara investigator.; Shoesmith Christen investigator.; Bartha Robart investigator.; Rademakers Rosa investigator.; Poos Jackie investigator.; Papma Janne M. investigator.; Giannini Lucia investigator.; van Minkelen Rick investigator.; Pijnenburg Yolande investigator.; Nacmias Benedetta investigator.; Ferrari Camilla investigator.; Polito Cristina investigator.; Lombardi Gemma investigator.; Bessi Valentina investigator.; Veldsman Michele investigator.; Andersson Christin investigator.; Thonberg Hakan investigator.; Öijerstedt Linn investigator.; Jelic Vesna investigator.; Thompson Paul investigator.; Langheinrich Tobias investigator.; Lladó Albert investigator.; Antonell Anna investigator.; Olives Jaume investigator.; Balasa Mircea investigator.; Bargalló Nuria investigator.; Borrego‐Ecija Sergi investigator.; Verdelho Ana investigator.; Maruta Carolina investigator.; Ferreira Catarina B. investigator.; Miltenberger Gabriel investigator.; do Couto Frederico Simões investigator.; Gabilondo Alazne investigator.; Gorostidi Ana investigator.; Villanua Jorge investigator.; Cañada Marta investigator.; Tainta Mikel investigator.; Zulaica Miren investigator.; Barandiaran Myriam investigator.; Alves Patricia investigator.; Bender Benjamin investigator.; Wilke Carlo investigator.; Graf Lisa investigator.; Vogels Annick investigator.; Vandenbulcke Mathieu investigator.; Van Damme Philip investigator.; Bruffaerts Rose investigator.; Poesen Koen investigator.; Rosa‐Neto Pedro investigator.; Gauthier Serge investigator.; Camuzat Agnès investigator.; Brice Alexis investigator.; Bertrand Anne investigator.; Funkiewiez Aurélie investigator.; Rinaldi Daisy investigator.; Saracino Dario investigator.; Colliot Olivier investigator.; Sayah Sabrina investigator.; Prix Catharina investigator.; Wlasich Elisabeth investigator.; Wagemann Olivia investigator.; Loosli Sandra investigator.; Schönecker Sonja investigator.; Hoegen Tobias investigator.; Lombardi Jolina investigator.; Anderl‐Straub Sarah investigator.; Rollin Adeline investigator.; Kuchcinski Gregory investigator.; Bertoux Maxime investigator.; Lebouvier Thibaud investigator.; Deramecourt Vincent investigator.; Santiago Beatriz investigator.; Duro Diana investigator.; Leitão Maria João investigator.; Almeida Maria Rosario investigator.; Tábuas‐Pereira Miguel investigator.; Afonso Sónia investigator.;
• Is Part Of: Annals of clinical and translational neurology. Volume 9:Issue 11(2022)
• Page Start: 1764
• Page End: 1777
• Publication Date: 2022-10-17
• Subjects: Nervous system -- Diseases -- Periodicals; Neurology -- Periodicals; 616.8005
• DOI: 10.1002/acn3.51672
• Languages: English
• ISSNs: 2328-9503

Abstract

Abstract: 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 95 th 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.