α-Synuclein and DJ-1 as Potential Biological Fluid Biomarkers for Parkinson’s Disease

Abstract

Parkinson’s disease (PD) is the most common form of movement disorder and affects approximately 4% of the population aged over 80 years old. Currently, PD cannot be prevented or cured, and no single diagnostic biomarkers are available. Notably, recent studies suggest that two familial PD-linked molecules, α-synuclein and DJ-1, are present in cerebrospinal fluid (CSF) and that their levels may be altered during the progression of PD. In this regard, sensitive and accurate methods for evaluation of α-synuclein and DJ-1 levels in the CSF and blood have been developed, and the results suggest that the levels of both molecules are significantly decreased in the CSF in patients with PD compared with age-matched controls. Furthermore, specific detection and quantification of neurotoxic oligometric forms of α-synuclein in the blood using enzyme-linked immunosorbent assays might be expected as potential peripheral biomarkers for PD, although further validation is required. Currently, neither α-synuclein nor DJ-1 is satisfactory as a single biomarker for PD, but combinatory evaluation of these biological fluid molecules with other biomarkers and imaging techniques may provide reliable information for diagnosis of PD.

Parkinson’s Disease

“…A number of current reviews summarize the range of technologies being pursued in the search for biomarkers in PD (Disease Study Group 2010; Dorsey et al 2006, 2008; Waragai et al 2010). The focus here will be on cerebrospinal fluid (CSF) α-synuclein and related proteins and plasma markers.…”

“…Numerous studies have examined whether immune indices measured in plasma or CSF might serve as molecular markers of disease risk, presence and progression (McGeer et al 1988; Teismann et al 2003; Michell et al 2004; Chen et al 2008a; Stefanova et al 2009). A host of various molecules have been studied: IL-2, IL-4, IL-6, IL-10, TNF-α, IFN-γ, as well as oxidative stress related substances: reactive oxygen species, proinflammatory prostaglandins and cytokines (Brodacki et al 2008; Waragai et al 2010). Although studies have revealed elevated levels of various cytokines and trophic molecules in PD, these observations have yet to provide a means to segregate disease phenotypes or to monitor disease progression.…”

Blood and cerebrospinal fluid markers in Parkinson's disease: current biomarker findings

“…12 and plasma, [13][14][15] and decreased CSF α-synuclein levels in PD have now been demonstrated in a number of studies. 12,[16][17][18][19][20][21][22][23] Two of these studies examined patients with early PD, making it unlikely that results are simply associated with anti-PD medication effects. 22,23 These studies have raised hopes that α-synuclein could be a first diagnostic marker for PD.…”

DJ-1 isoforms in whole blood as potential biomarkers of Parkinson disease

“…More than 95% of blood DJ-1 is contained in RBCs12, and variable in vitro or in vivo hemolytic changes that are beyond investigators' control likely contributed to contradicting reports in the literature regarding its plasma levels12212223. Our study has the advantage that it was carried out in whole blood, eliminating the possibility of confounding by component contamination.…”