Abstract
The diagnosis of Parkinson’s disease (PD) remains primarily a clinical issue, based mainly on phenotypic patterns. The identification of biomarkers capable of permitting the preclinical detection of PD is critically needed. α-Synuclein is a key protein in PD, with missense and multiplication mutations in the gene encoding α-synuclein (SNCA) having been reported in familial cases of PD, and accumulation of the protein identified in Lewy bodies (LBs) and Lewy neurites (LNs) in affected brain regions. With the objective of validating the use of α-synuclein as a clinical or progressive biomarker in an accessible tissue, we used an enzyme-linked immunosorbent assay (ELISA) to measure α-synuclein levels in the peripheral blood plasma of idiopathic PD and LRRK2 mutation carrier patients and compared our findings with healthy control subjects. Compared to healthy controls, we found a significant decrease in plasma total α-synuclein levels in idiopathic PD (iPD) patients (n = 134, p = 0.010). However, the reduction was less significant in patients who were LRRK2 mutation carriers (n = 32, p = 0.133). This lack of significance could be due to the small number of individuals employed in this group. No predictive value of total α-synuclein in the diagnosis of PD was found in a receiver operating characteristic (ROC) curve analysis. Although this is a pilot study requiring corroboration on a larger cohort of patients, our results highlight the possible use of plasma α-synuclein as a biomarker for PD.
Highlights
While Parkinson’s disease (PD) is the second most common neurodegenerative disease in humans, its etiology remains largely unknown
Patients were classified as LRRK2 mutation carriers (n = 32) or non-mutation carriers (n = 134) according to both most prevalent LRRK2 screened mutations (G2019S, n = 4 and R1441G, n = 28)
Patients and controls did not differ in age (p = 0.139; Table 1), the proportion of males and females did differ between groups (p = 0.013)
Summary
While Parkinson’s disease (PD) is the second most common neurodegenerative disease in humans, its etiology remains largely unknown. The diagnosis of PD remains a clinical entity based on the presence of the cardinal motor signs. Reliable diagnostic markers would be valuable even in the pre-motor stage of the disease, if disease modifying agents become available. Most PD patients have the idiopathic form of the disease (iPD), familial PD cases have been widely reported. PD associated with LRRK2 mutations is the most common known genetic cause of autosomal dominant PD [2,3,4]. These cases commonly have a late onset and a typical clinical picture of iPD. The most frequent LRRK2 mutation, G2019S, has been identified throughout the world, while others, like R1441G, show a more geographically specific localization, mainly in northern Spain [5,6,7,8]
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