Inference of Diagnostic Markers and Therapeutic Targets from CSF proteomics for the Treatment of Hydrocephalus

The purpose of this mini-review is to examine if publicly available cerebrospinal fluid (CSF) proteomics data sets can be exploited to provide insight into the etiology of hydrocephalus, into the character of the injury inflicted on the parenchyma by ventriculomegaly, and into the response of the brain to this condition. While this undertaking was instigated by reanalysis of recent comparative proteomics of CSF collected from the brain of healthy and Mpdz knockout (KO) mice (Yang et al., 2019), it is an opportunity to survey previously published CSF proteomics data sets to determine if they can be pooled together to that end. The overabundance of extracellular matrix (ECM) proteins, complement factors, and apolipoproteins in the CSF of Mpdz KO mice was taken to indicate that the hydrocephalic brain underwent ischemia, inflammation, and demyelination. The overabundance of five cytokine-binding proteins could be linked uniquely to insulin-like growth factor (IGF) secretion and signaling. The overabundance of two serpins, angiotensinogen and pigment epithelium-derived factor (PEDF) was considered as a biomarker of anti-angiogenic negative-feedback mechanisms to reduce CSF production. These findings raise the intriguing propositions that CSF proteomics can identify biomarkers of case-specific injuries, and that IGF signaling and angiogenesis pathways can serve as therapeutic targets. It appears, however, that the currently available proteomics data is not amenable to comparison of CSF from normal and hydrocephalic patients and cannot be used test the premise of those propositions.