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