Serum glial fibrillary acidic protein is a marker of disease severity in 1 frontotemporal lobar degeneration

46 Objective: To assess the diagnostic and prognostic value of serum glial fibrillary acidic protein 47 (GFAP) in a large cohort of patients with frontotemporal lobar degeneration (FTLD). 48 Methods: In this retrospective study, performed on 406 participants, we measured serum GFAP 49 concentration with an ultrasensitive Single molecule array (Simoa) method in FTLD, Alzheimer’s 50 disease (AD) and healthy ageing. We assessed the role of GFAP as marker of disease severity by 51 analysing the correlation with clinical variables, neurophysiological data and cross-sectional brain 52 imaging. Moreover, we evaluated the role of serum GFAP as a prognostic marker of disease 53 survival. 54 Results: We observed significantly higher levels of serum GFAP in patients with FTLD 55 syndromes, except progressive supranuclear palsy (PSP), compared with healthy controls, but not 56 compared with AD patients. In FTLD, serum GFAP levels correlated with measures of cognitive 57 dysfunction and disease severity, and were associated with indirect measures of GABAergic deficit. 58 Serum GFAP concentration was not a significant predictor of survival. 59 Conclusions: Serum GFAP is a marker of disease severity in FTLD. 60