290 CSF chitinases as novel biomarkers for MND

    loading  Checking for direct PDF access through Ovid


The development of biomarkers for amyotrophic lateral sclerosis (ALS, the commonest phenotype of MND) is a priority to reduce diagnostic delay, allow earlier assessment of therapeutic activity, and provide pathogenic insight.Liquid chromatography tandem mass spectrometry with label-free quantification was used to quantify CSF proteins in individual participant samples. A longitudinal cohort comprised patients with ALS (n=43) and primary lateral sclerosis (PLS, n=6). A cross-sectional cohort comprised healthy (n=20) and disease control patient CSF samples (Parkinson’s disease n=20, MND mimic disorders n=12).Among 773 identified proteins, significantly elevated levels of three macrophage-derived chitinase proteins were detected in the ALS group, specifically chitotriosidase (CHIT1), chitinase-3-like protein 1 (CHI3L1) and chitinase-3-like protein 2 (CHI3L2). Levels correlated with rate of disease progression (CHIT1 r=0.56, p<0.001; CHI3L1 r=0.31, p=0.028; CHI3L2 r=0.29, p=0.044), and levels of the axonal degeneration marker phosphorylated neurofilament heavy chain (r=0.62, p<0.001; r=0.49, p<0.001; r=0.41, p<0.001). Levels of CHI3L1, but not CHIT1 or CHI3L2, increased over time in those with low initial values (gradient=0.005 log abundance units/month, p=0.001).Microglial activation has been implicated in the pathogenesis of MND and neuroinflammatory pathways are a major target of therapeutic interest. CSF chitinases may be potential pharmacodynamic as well as diagnostic biomarkers.

    loading  Loading Related Articles