Salivary α-synuclein and DJ-1: potential biomarkers for Parkinson's disease

Abstract

Sir, Parkinson's disease is a neurodegenerative disorder belonging to a group of heterogeneous diseases characterized by a progressive and relatively selective loss of anatomically or physiologically related neuronal systems (Lang and Lozano, 1998; Silvers and Som, 1998). The identification of Parkinson's disease specific biomarkers, particularly at early stages, is critical for Parkinson's disease diagnosis, monitoring disease progression and patient management as well as the development of therapeutic interventions. Thus far, the proteins α-synuclein (α-Syn) and DJ-1 have been tested rigorously in Parkinson's disease. In our recent study published in Brain (Hong et al., 2010), where a large cohort of patients with Parkinson's disease and controls were included, we provided evidence that α-Syn, along with DJ-1, decreases in Parkinson's disease CSF, providing high sensitivity and specificity for Parkinson's disease diagnosis. However, even though CSF is close to the main site of pathology in Parkinson's disease and other neurodegenerative disorders in the CNS, it cannot be readily obtained in most clinical settings (Shi et al., 2010). To address this issue, several groups have examined serum/plasma concentrations of α-Syn and DJ-1 as potential biomarkers of Parkinson's disease. Unfortunately, a major drawback in assessing serum/plasma α-Syn and DJ-1 levels is the fact that >95% of total blood α-Syn and DJ-1 are derived from red blood cells. After controlling for several major variables, we concluded in a recent investigation that, unlike CSF, these two markers in plasma are unable to differentiate patients with Parkinson's disease from controls (Shi et al., 2010). Of note, blood contamination of human CSF is also a major problem when assessing levels of α-Syn and DJ-1 in CSF (Hong et al., 2010; Shi et al., 2010).