PT  - JOURNAL ARTICLE
AU  - Heller, Carolin
AU  - Foiani, Martha S
AU  - Moore, Katrina
AU  - Convery, Rhian
AU  - Bocchetta, Martina
AU  - Neason, Mollie
AU  - Cash, David M
AU  - Thomas, David
AU  - Greaves, Caroline V
AU  - Woollacott, Ione OC
AU  - Shafei, Rachelle
AU  - Van Swieten, John C
AU  - Moreno, Fermin
AU  - Sanchez-Valle, Raquel
AU  - Borroni, Barbara
AU  - Laforce Jr, Robert
AU  - Masellis, Mario
AU  - Tartaglia, Maria Carmela
AU  - Graff, Caroline
AU  - Galimberti, Daniela
AU  - Rowe, James B
AU  - Finger, Elizabeth
AU  - Synofzik, Matthis
AU  - Vandenberghe, Rik
AU  - de Mendonca, Alexandre
AU  - Tagliavini, Fabrizio
AU  - Santana, Isabel
AU  - Ducharme, Simon
AU  - Butler, Christopher R
AU  - Gerhard, Alex
AU  - Levin, Johannes
AU  - Danek, Adrian
AU  - Frisoni, Giovanni
AU  - Sorbi, Sandro
AU  - Otto, Markus
AU  - Heslegrave, Amanda J
AU  - Zetterberg, Henrik
AU  - Rohrer, Jonathan D
ED  - , 
TI  - Plasma glial fibrillary acidic protein is raised in progranulin-associated frontotemporal dementia
AID  - 10.1136/jnnp-2019-321954
DP  - 2020 Mar 01
TA  - Journal of Neurology, Neurosurgery & Psychiatry
PG  - 263--270
VI  - 91
IP  - 3
4099  - http://jnnp.bmj.com/content/91/3/263.short
4100  - http://jnnp.bmj.com/content/91/3/263.full
SO  - J Neurol Neurosurg Psychiatry2020 Mar 01; 91
AB  - 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.