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Research Paper|Volume 10, Issue 9|pp 2367—2382

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

Pol Andrés-Benito1,2,3, Raúl Domínguez4, Maria J. Colomina5, Franc Llorens2,3, Mònica Povedano4, Isidre Ferrer1,2,3,6,7
  • 1Department of Pathology and Experimental Therapeutics, University of Barcelona, L’Hospitalet de Llobregat, Barcelona, Spain
  • 2Biomedical Network Research Center on Neurodegenerative Diseases (CIBERNED), Institute Carlos III, L’Hospitalet de Llobregat, Barcelona, Spain
  • 3Bellvitge Biomedical Research Institute (IDIBELL), L’Hospitalet de Llobregat, Barcelona, Spain
  • 4Functional Unit of Amyotrophic Lateral Sclerosis (UFELA), Service of Neurology, Bellvitge University Hospital, L’Hospitalet de Llobregat, Barcelona, Spain
  • 5Anesthesia and Critical Care Department, Bellvitge University Hospital - University of Barcelona L’Hospitalet de Llobregat, Barcelona, Spain
  • 6Neuropathology, Pathologic Anatomy Service, Bellvitge University Hospital, IDIBELL, L’Hospitalet de Llobregat, Barcelona, Spain
  • 7Institute of Neurosciences, University of Barcelona, Barcelona, Spain
Received: July 21, 2018Accepted: September 6, 2018Published: September 13, 2018
https://doi.org/10.18632/aging.101551

Copyright: © 2018 Andrés-Benito et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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 (P=0.004) in sporadic ALS (sALS) cases when compared with age-matched controls. These correlate with increased mRNA expression of microglial markers AIF1 and CD68 in the spinal cord in sALS (P=0.044 and P=0.000, respectively). YKL40 mRNA and protein expression had a tendency to increase in post-mortem frontal cortex area 8 (P=0.06 and P=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) (P=0.045). Higher levels are found in patients with fast progression when compared with patients with slow and normal progression (P=0.008 and P=0.004, respectively), and correlates with ALS-FRS-R slope (P=0.000). Additionally, increased protein levels of neurofilament light chain (NF-L) are also found in sALS (P=0.000); highest values are found in patients with fast progression when compared with cases with slow and normal progression (P=0.005 and P=0.000, respectively), and also correlate with ALS-FRS-R slope (P=0.000). Pearson’s correlation test linked positively the increased levels of YKL40 with increased NF-L levels (P=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.