Plasma glial fibrillary acidic protein is raised in progranulin-associated frontotemporal dementia
Creators: name: Heller, Carolin
name: Foiani, Martha S
name: Moore, Katrina
name: Convery, Rhian
name: Bocchetta, Martina
name: Neason, Mollie
name: Cash, David M
name: Thomas, David
name: Greaves, Caroline V
name: Woollacott, Ione OC
name: Shafei, Rachelle
name: Van Swieten, John C
name: Moreno, Fermin
name: Sanchez-Valle, Raquel
name: Borroni, Barbara
name: Laforce Jr, Robert
name: Masellis, Mario
name: Tartaglia, Maria Carmela
name: Graff, Caroline
name: Galimberti, Daniela
name: Rowe, James B
name: Finger, Elizabeth
name: Synofzik, Matthis
name: Vandenberghe, Rik
name: De Mendonca, Alexandre
name: Tagliavini, Fabrizio
name: Santana, Isabel
name: Ducharme, Simon
name: Butler, Christopher R
name: Gerhard, Alex
name: Levin, Johannes
name: Danek, Adrian
name: Frisoni, Giovanni
name: Sorbi, Sandro
name: Otto, Markus
name: Heslegrave, Amanda J
name: Zetterberg, Henrik
name: Rohrer, Jonathan D
Publisher: name: Apollo - University of Cambridge Repository
Year: 2020
Subjects: Neurodegeneration

description: Funder: Bluefield project
description: Funder: Weston Brain Institute; FundRef: http://dx.doi.org/10.13039/100012479
description: Funder: Alzheimer Nederland; FundRef: http://dx.doi.org/10.13039/501100010969
description: Funder: Brain Research Trust; FundRef: http://dx.doi.org/10.13039/501100000368
description: Funder: Stockholm County Council ALF
description: Funder: Association for Frontotemporal Degeneration; FundRef: http://dx.doi.org/10.13039/100003607
description: Funder: Hjärnfonden; FundRef: http://dx.doi.org/10.13039/501100003792
description: Funder: Swedish FTD Initiative-Schörling Foundation
description: Funder: EU Joint Programme - Neurodegenerative Disease Research; Grant(s): 2018-02754, Prefrontals VR Dnr 529-2014-7504, VR: 2015-02926
description: Funder: Alzheimer Foundation
description: Funder: Ontario Brain Institute; FundRef: http://dx.doi.org/10.13039/100008914
description: Funder: Center for Networked Biomedical Research on Neurodegenerative Disease (CIBERNED)
description: Funder: Tau Consortium
description: Funder: UK Dementia Research Institute UCL
description: Background: There are few validated fluid biomarkers in frontotemporal dementia (FTD). Glial fibrillary acidic protein (GFAP) is a measure of astrogliosis, a known pathological process of FTD, but has yet to be explored as potential biomarker. Methods: Plasma GFAP and neurofilament light chain (NfL) concentration were measured in 469 individuals enrolled in the Genetic FTD Initiative: 114 C9orf72 expansion carriers (74 presymptomatic, 40 symptomatic), 119 GRN mutation carriers (88 presymptomatic, 31 symptomatic), 53 MAPT mutation carriers (34 presymptomatic, 19 symptomatic) and 183 non-carrier controls. Biomarker measures were compared between groups using linear regression models adjusted for age and sex with family membership included as random effect. Participants underwent standardised clinical assessments including the Mini-Mental State Examination (MMSE), Frontotemporal Lobar Degeneration-Clinical Dementia Rating scale and MRI. Spearman’s correlation coefficient was used to investigate the relationship of plasma GFAP to clinical and imaging measures. Results: Plasma GFAP concentration was significantly increased in symptomatic GRN mutation carriers (adjusted mean difference from controls 192.3 pg/mL, 95% CI 126.5 to 445.6), but not in those with C9orf72 expansions (9.0, –61.3 to 54.6), MAPT mutations (12.7, –33.3 to 90.4) or the presymptomatic groups. GFAP concentration was significantly positively correlated with age in both controls and the majority of the disease groups, as well as with NfL concentration. In the presymptomatic period, higher GFAP concentrations were correlated with a lower cognitive score (MMSE) and lower brain volume, while in the symptomatic period, higher concentrations were associated with faster rates of atrophy in the temporal lobe. Conclusions: Raised GFAP concentrations appear to be unique to GRN-related FTD, with levels potentially increasing just prior to symptom onset, suggesting that GFAP may be an important marker of proximity to onset, and helpful for forthcoming therapeutic prevention trials.