Biochemical Biomarkers

Various biochemical factors are being studied as possible biomarkers of Parkinson's disease (Graeber, 2009). Candidate biochemical biomarkers include alpha-synuclein expression in skin fibroblasts (Hoepken et al., 2008) and levels in cerebral spinal fluid (CSF) and blood (El-Agnaf et al., 2006; Mollenhauer et al., 2008). The validity of alpha-synuclein in the blood or CSF of PD patients as a diagnostic or an index of disease progression remains controversial (Ohrfelt et al., 2009) and further cross-sectional and longitudinal studies are warranted. In addition to the observation of alpha-synuclein in biofluids, another PD-related protein, DJ-1, has also been detected in blood and CSF (Waragai et al., 2007; Waragai et al., 2006). Refinement of detection methods for both analytes is necessary to confirm these observations.

In addition to the genetically-associated proteins alpha-synuclein and DJ-1, multiple other markers associated with putative disease-related processes such as oxidative stress and protein folding have been observed to be altered in PD subjects compared to controls. These include 8-OHdG (8-hydroxy-2-deoxyguanosine) (Bogdanov et al., 2008), serum urate (Schwarzschild et al., 2008), and H-FAMP (Wada-Isoe et al., 2008). Multi-gene mRNA expression analysis of blood may also reveal transcript changes associated with protein folding (Scherzer et al., 2007).

Other possible biomarkers have been identified in CSF, including beta-amyloid(1-42) and tau (Parnetti et al., 2008) and a multianalyte profile including tau, BDNF, IL-8, Abeta42, beta2-microglobulin, vitamin D binding protein apo AII and ApoE (Zhang et al., 2008).

Longitudinal testing to confirm the validity of these proteins as markers of disease progression may aid identification of at-risk individuals prior to the emergence of the cardinal motor symptoms of PD.