BACKGROUND AND PURPOSE: Neurofilament light chain (NfL) has recently been 
proposed as a promising biomarker in frontotemporal dementia (FTD). We 
investigated the correlation of both cerebrospinal fluid (CSF) and serum NfL 
with detailed neuropsychological data and cognitive decline in a cohort of 
sporadic and familial FTD.
METHODS: CSF and serum NfL, as well as conventional CSF Alzheimer's disease (AD) 
biomarkers (Aβ42, t-Tau, p-Tau181), were determined in 63 FTD patients (30 
sporadic-FTD, 20 with progranulin (GRN) mutations [FTD-GRN], 13 with chromosome 
9 open reading frame 72 [C9orf72] expansions [C9orf72-FTD]), 37 AD patients, and 
31 neurologic controls. Serum NfL was also quantified in 37 healthy individuals. 
Correlations between baseline CSF and serum NfL levels, standardized 
neuropsychological tests, and the rate of cognitive decline in FTD patients were 
assessed.
RESULTS: CSF and serum NfL presented with significantly higher levels in FTD 
than in AD patients and both control groups. Within FTD subtypes, genetic cases, 
and particularly FTD-GRN, had higher CSF and serum NfL levels. Significant 
correlations between NfL levels and overall cognitive function, abstract 
reasoning (CSF and serum), executive functions, memory, and language (serum) 
were found. A relationship between increased baseline CSF and serum NfL and a 
decay in cognitive performance over time was also observed.
CONCLUSIONS: Our findings highlight the potential of serum NfL as a useful 
surrogate end point of disease severity in upcoming targeted treatments.