Biomarkers of central nervous system inflammation in infantile and juvenile gangliosidoses

Mol Genet Metab. 2015 Feb;114(2):274-80. doi: 10.1016/j.ymgme.2014.11.015. Epub 2014 Dec 6.


The gangliosidoses (Tay-Sachs disease, Sandhoff disease, and GM1-gangliosidosis) are progressive neurodegenerative diseases caused by lysosomal enzyme activity deficiencies and consequent accumulation of gangliosides in the central nervous system (CNS). The infantile forms are distinguished from the juvenile forms by age of onset, rate of disease progression, and age of death. There are no approved treatments for the gangliosidoses. In search of potential biomarkers of disease, we quantified 188 analytes in CSF and serum from living human patients with longitudinal (serial) measurements. Notably, several associated with inflammation were elevated in the CSF of infantile gangliosidosis patients, and less so in more slowly progressing forms of juvenile gangliosidosis, but not in MPS disease. Thirteen CSF and two serum biomarker candidates were identified. Five candidate biomarkers were distinguished by persistent elevation in the CSF of patients with the severe infantile phenotype: ENA-78, MCP-1, MIP-1α, MIP-1β, and TNFR2. Correspondence of abnormal elevation with other variables of disease-i.e., severity of clinical phenotype, differentiation from changes in serum, and lack of abnormality in other neurodegenerative lysosomal diseases-identifies these analytes as biomarkers of neuropathology specific to the gangliosidosis diseases.

Keywords: GM1-gangliosidosis; Ganglioside; Glycosphingolipid; Metabolomic; Sandhoff disease; Tay–Sachs disease.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Biomarkers / blood
  • Biomarkers / cerebrospinal fluid*
  • Central Nervous System / metabolism
  • Chemokine CCL2 / cerebrospinal fluid
  • Chemokine CCL4 / cerebrospinal fluid
  • Chemokine CXCL5 / cerebrospinal fluid
  • Child
  • Child, Preschool
  • Female
  • Gangliosidoses / diagnosis*
  • Gangliosidoses / metabolism
  • Gangliosidosis, GM1 / diagnosis
  • Gangliosidosis, GM1 / metabolism
  • Humans
  • Infant
  • Inflammation / diagnosis*
  • Male
  • Receptors, Tumor Necrosis Factor, Type II / cerebrospinal fluid
  • Sandhoff Disease / diagnosis
  • Sandhoff Disease / metabolism
  • Tay-Sachs Disease / diagnosis
  • Tay-Sachs Disease / metabolism
  • Transcription Factors / cerebrospinal fluid


  • Biomarkers
  • CCL2 protein, human
  • CXCL5 protein, human
  • Chemokine CCL2
  • Chemokine CCL4
  • Chemokine CXCL5
  • MNP-1 protein, human
  • Receptors, Tumor Necrosis Factor, Type II
  • Transcription Factors