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290 CSF chitinases as novel biomarkers for MND
  1. Thompson Alexander G1,
  2. Gray Elizabeth1,
  3. Thézénas Marie-Laetitia2,
  4. Charles Philip D2,
  5. Evetts Samuel1,
  6. Hu Michele T1,
  7. Talbot Kevin1,
  8. Fischer Roman2,
  9. Kessler Benedikt M2,
  10. Turner Martin R2
  1. 1Nuffield Department of Clinical Neurosciences, University of Oxford
  2. 2Target Discovery Institute, Nuffield Department of Medicine, University of Oxford


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.

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