YKL40 in sporadic amyotrophic lateral sclerosis: cerebrospinal fluid levels as a prognosis marker of disease progression

Abstract

Amyotrophic lateral sclerosis (ALS) has variable clinical course and fatal outcome. Since inflammation plays a role in the pathogenesis of ALS, chitinase-3-like protein 1 or YKL40 has been assessed as putative biomarker of disease progression. YKL40 mRNA levels are increased in anterior horn of the spinal cord (<i>P=</i>0.004) in sporadic ALS (sALS) cases when compared with age-matched controls. These correlate with increased mRNA expression of microglial markers <i>AIF1</i> and <i>CD68</i> in the spinal cord in sALS (<i>P=</i>0.044 and <i>P=</i>0.000, respectively). YKL40 mRNA and protein expression had a tendency to increase in post-mortem frontal cortex area 8 (<i>P=</i>0.06 and <i>P=</i>0.08, respectively). Yet YKL40 immunoreactivity is restricted to a subpopulation of astrocytes in these regions. YKL40 protein levels, as revealed by enzyme-linked immunosorbent assay (ELISA), are significantly increased in the CSF in sALS (n=86) compared with age-matched controls (n=21) (<i>P</i>=0.045). Higher levels are found in patients with fast progression when compared with patients with slow and normal progression (<i>P</i>=0.008 and <i>P</i>=0.004, respectively), and correlates with ALS-FRS-R slope (<i>P</i>=0.000). Additionally, increased protein levels of neurofilament light chain (NF-L) are also found in sALS (<i>P</i>=0.000); highest values are found in patients with fast progression when compared with cases with slow and normal progression (<i>P</i>=0.005 and <i>P</i>=0.000, respectively), and also correlate with ALS-FRS-R slope (<i>P</i>=0.000). Pearson's correlation test linked positively the increased levels of YKL40 with increased NF-L levels (<i>P</i>=0.013). These data point to YKL40 and NF-L protein levels in the CSF as a good biomarker combination of disease progression in sALS.