The goal of this study was to determine the ability of plasma neurofilament light chain (NfL) to predict disease progression over two years in autosomal dominant frontotemporal lobar degeneration (FTLD).

At baseline, median NfL levels were lower in asymptomatic mutation carriers (7.3±5 pg/mL) than in prodromal disease (12.1±10 pg/mL, P<0.005), but were higher in individuals who converted to prodromal disease or full phenotype (10.6±8 pg/mL) as compared to non-converters (6.7±4 pg/mL, P=0.038). Cross-sectionally, NfL levels correlated most strongly with measures of severity including the FTLD-CDRsb score (b=0.6, P=8.2 x 10^-28), but also with a variety of neuropsychological scales and regional MRI volumes. In asymptomatic carriers, but not in non-carriers, NfL correlated with frontotemporal gray matter volumes. Over two years of follow up, elevated baseline NfL predicted worsening in measures of disease severity (P=4.0 x 10^-6), instrumental activities (P=2.4 x 10^-4), activities of daily living (P=0.045) and executive function (P=0.003), regardless of genotype. In prodromal disease, NfL predicted rates of decline in memory, executive function and gray matter volume loss. 

Plasma NfL identifies asymptomatic carriers of FTLD-causing mutations at risk for conversion to symptomatic status, and may be a useful tool to identify participants for prevention clinical trials and assess response to experimental therapies.