CSF-Based Analysis for Identification of Potential Serum Biomarkers of Neural Tube Defects

The protein composition of cerebrospinal fluid (CSF) in neural tube defects (NTDs) remains unknown. We investigated the protein composition of CSF from 9 infants with NTDs using isobaric tags for relative and absolute quantitation (iTRAQ). We identified 568 proteins in the CSF of infants with spina bifida, which is the most common type of NTD. Among these, 18 proteins were associated with neural tube closure in the CSF during human embryonic neurulation and 5 were involved in NTDs. Based on these results, an animal model was further utilized to investigate early serum biomarkers for NTDs. We found that the myristoylated alanine-rich C-kinase substrate, Kunitz-type protease inhibitor 2, and apolipoprotein B-100 protein levels were decreased in both embryos and the sera of pregnant Sprague-Dawley rats carrying embryos with NTDs. CSF proteins may be useful in the discovery of potential serum biomarkers for NTDs.