Recent advances in CSF biomarkers for Parkinson's disease

Though the search for cerebrospinal fluid (CSF) biomarkers of Parkinson's disease (PD) began more than 40 years ago, the most promising results are relatively recent. Disease-specific indicators have been sought among the hundreds of proteins and other biochemicals found in CSF (which is contiguous with the extracellular fluid compartment of the brain). Initially, research focused on the selective neurotransmitter disturbance in PD. While investigations of dopamine metabolism (as reflected by its major metabolite, homovanillic acid [HVA]) have been relatively uninformative, we found that indexing HVA concentration to that of the purine metabolite xanthine permits differentiation of PD specimens from healthy controls (p < 0.0016) [Brain Research 2011;1408:88-97]. In another recent biomarker study, we utilized ultrahigh-performance liquid chromatography linked to gas chromatography-mass spectrometry for metabolomic analysis [Movement Disorders 2011;26(Suppl 2):S193]. Using t-tests to differentiate PD and control groups at p < 0.02, we found changes in compounds not known to be related to the neurodegenerative process (4 increased in CSF concentration and 8 decreased). Other recent investigations have reported distinctive biomarker findings in proteins and other biochemicals. The ultimate goal is for CSF biomarkers also found in peripheral biospecimens, aiding in diagnostic screening applications and providing further clues as to the etiology of PD.