Abstract Background Clinical proteomics has been widely used to identify differentially displayed proteins in blood and cerebrospinal fluid (CSF) to understand the molecular and cellular events leading to Parkinson's disease (PD). The close connection between CSF and the brain offers reliable and reproducible way to assess the majority of changes in the brain proteome profile directly into CSF throughout the course of neurodegeneration. Methods We identified the differentially displayed proteins in CSF of PD patients as compared with controls using two-dimensional polyacrylamide gel electrophoresis (2-D PAGE) and mass spectrometry. Results Comparative 2-D PAGE electrophoretograms of CSF of PD patients with case controls and/or neurological controls revealed significant differential display of six protein spots. The differentially displayed proteins were identified as serum albumin precursor, serum albumin chain-A, hemoglobin β fragment, mutant globin, proline rich repeat 14 (PRR 14) and serum transferrin N-terminal lobe. Although the level of hemoglobin β fragment and mutant globin was attenuated, serum albumin precursor, serum albumin chain-A, PRR 14 and serum transferrin N-terminal lobe were augmented in PD patients as compared with case controls. The level of serum albumin chain-A, PRR 14 and serum transferrin N-terminal lobe was not significantly altered when compared with neurological controls. Conclusions The results obtained thus suggest that differential display of CSF serum albumin precursor, serum albumin chain-A, PRR 14 and serum transferrin N-terminal lobe could be associated with neuronal dysfunction and hemoglobin/globin with the onset/progression of PD in humans.