| Title: |
CSF glial markers are elevated in a subset of patients with genetic frontotemporal dementia |
| Authors: |
Woollacott, IOC; Swift, IJ; Sogorb‐Esteve, A; Heller, C; Knowles, K; Bouzigues, A; Russell, LL; Peakman, G; Greaves, CV; Convery, R; Heslegrave, A; Thonberg, H; Öijerstedt, L; Jelic, V; Loosli, S; Thompson, P; Rowe, JB; Langheinrich, T; Lladó, A; Antonell, A; Olives, J; Kuchcinski, G; Balasa, M; Rosa‐Neto, P; Miltenberger, G; Bargalló, N; do Couto, FS; Gabilondo, A; Tainta, M; Schönecker, S; Gauthier, S; Zulaica, M; Bertoux, M; Barandiaran, M; Alves, P; Bender, B; van Swieten, JC; Wilke, C; Hoegen, T; Graf, L; Vogels, A; Vandenbulcke, M; Van Damme, P; Lebouvier, T; Camuzat, A; Borroni, B; Lombardi, J; Brice, A; Seelaar, H; Bertrand, A; Funkiewiez, A; Rinaldi, D; Levin, J; Saracino, D; Cope, T; Galimberti, D; Colliot, O; Sayah, S; Prix, C; Wlasich, E; Jiskoot, L; Anderl‐Straub, S; Wagemann, O; Tiraboschi, P; Rollin, A; Deramecourt, V; Otto, M; Sorbi, S; Santiago, B; Duro, D; Leitão, MJ; Almeida, MR; Cantoni, V; Tábuas‐Pereira, M; Pasquier, F; Masellis, M; Afonso, S; Tartaglia, MC; Finger, E; Butler, CR; Rittman, T; Santana, I; Graff, C; Arighi, A; Gerhard, A; Laforce, R; Sanchez‐Valle, R; Rogaeva, E; de Mendonça, A; Benussi, A; Moreno, F; Synofzik, M; Vandenberghe, R; Ducharme, S; Fenoglio, C; Zetterberg, H; Ber, IL; Premi, E; Rohrer, JD; Castelo‐Branco, M; Nelson, A; Bocchetta, M; Cash, D; Ferrari, C; Thomas, DL; Borrego‐Ecija, S; Todd, E; Benotmane, H; Nicholas, J; Samra, K; Shafei, R; Freedman, M; Gasparotti, R; Timberlake, C; Archetti, S; Gazzina, S; Scarpini, E; Polito, C; Keren, R; Fumagalli, G; Borracci, V; Rossi, G; Giaccone, G; Gorostidi, A; Di Fede, G; Lombardi, G; Caroppo, P; Prioni, S; Redaelli, V; Tang‐Wai, D; Black, S; Verdelho, A; Bessi, V; Mitchell, S; Villanua, J; Shoesmith, C; Bartha, R; Rademakers, R; Bruffaerts, R; Poos, J; Maruta, C; Papma, JM; Giannini, L; van Minkelen, R; Pijnenburg, Y; Cañada, M; Veldsman, M; Nacmias, B; Ferreira, CB; Andersson, C; Poesen, K |
| Contributors: |
Genetic FTD Initiative, GENFI |
| Publisher Information: |
Wiley Periodicals LLC on behalf of American Neurological Association. |
| Publication Year: |
2022 |
| Collection: |
Brunel University London: Brunel University Research Archive (BURA) |
| Description: |
Data Availability Statement: Some GENFI data are available on reasonable request through application to the GENFI Data Access Committee. ; Copyright © 2022 The Authors. 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 ... |
| Document Type: |
article in journal/newspaper |
| File Description: |
1764 - 1777; Electronic |
| Language: |
English |
| Relation: |
Annals of Clinical and Translational Neurology; https://bura.brunel.ac.uk/handle/2438/25546; https://doi.org/10.1002/acn3.51672 |
| DOI: |
10.1002/acn3.51672 |
| Availability: |
https://bura.brunel.ac.uk/handle/2438/25546; https://doi.org/10.1002/acn3.51672 |
| Rights: |
Copyright © 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. ; https://creativecommons.org/licenses/by/4.0/ ; The Authors |
| Accession Number: |
edsbas.42470DF3 |
| Database: |
BASE |