RT Journal Article
SR Electronic
T1 Plasma glial fibrillary acidic protein is raised in progranulin-associated frontotemporal dementia
JF Journal of Neurology, Neurosurgery & Psychiatry
JO J Neurol Neurosurg Psychiatry
FD BMJ Publishing Group Ltd
SP 263
OP 270
DO 10.1136/jnnp-2019-321954
VO 91
IS 3
A1 Heller, Carolin
A1 Foiani, Martha S
A1 Moore, Katrina
A1 Convery, Rhian
A1 Bocchetta, Martina
A1 Neason, Mollie
A1 Cash, David M
A1 Thomas, David
A1 Greaves, Caroline V
A1 Woollacott, Ione OC
A1 Shafei, Rachelle
A1 Van Swieten, John C
A1 Moreno, Fermin
A1 Sanchez-Valle, Raquel
A1 Borroni, Barbara
A1 Laforce Jr, Robert
A1 Masellis, Mario
A1 Tartaglia, Maria Carmela
A1 Graff, Caroline
A1 Galimberti, Daniela
A1 Rowe, James B
A1 Finger, Elizabeth
A1 Synofzik, Matthis
A1 Vandenberghe, Rik
A1 de Mendonca, Alexandre
A1 Tagliavini, Fabrizio
A1 Santana, Isabel
A1 Ducharme, Simon
A1 Butler, Christopher R
A1 Gerhard, Alex
A1 Levin, Johannes
A1 Danek, Adrian
A1 Frisoni, Giovanni
A1 Sorbi, Sandro
A1 Otto, Markus
A1 Heslegrave, Amanda J
A1 Zetterberg, Henrik
A1 Rohrer, Jonathan D
YR 2020
UL http://jnnp.bmj.com/content/91/3/263.abstract
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.