Peripheral alpha-synuclein levels in patients with genetic and non-genetic forms of Parkinson's disease.

BACKGROUND: Variations of α-synuclein levels have been reported in serum and plasma in Parkinson's Disease (PD) Patients. METHODS: Serum and plasma were obtained from PD patients without known mutations (GU-PD, n = 124)), carriers of the A53T/G209A point mutation in the α-synuclein gene (SNCA) (n = 29), and respective age-/sex-matched controls. Levels of total α-synuclein were assessed using an in-house ELISA assay. RESULTS: A statistically significant increase of α-synuclein levels was found in serum, but not plasma, from GU-PD patients compared to healthy controls. A statistically significant decrease of α-synuclein levels was found in serum and plasma from symptomatic A53T mutation carriers compared to healthy controls. Plasma α-synuclein levels were modestly negatively correlated with UPDRS part III score and disease duration in A53T-PD patients. CONCLUSION: Increased α-synuclein levels in serum of GU-PD patients suggest a systemic deregulation of α-synuclein homeostasis in PD. The opposite results in A53T-PD highlight the complexity of α-synuclein homeostatic regulation in PD, and suggest the possibility of reduced expression of the mutant allele.

Paper-based device providing visual genetic signatures for precision medicine: application to breast cancer.

Genome-wide association studies have demonstrated that combinations of single nucleotide polymorphisms (SNPs), rather than individual SNPs, represent genetic signatures that correlate with heterogeneous and complex diseases. In this context, we developed a paper-based device that provides visual detection of a 10-SNP panel as a genetic signature associated with the risk for breast cancer. The method involves multiplex PCR amplification, multiplex extension reaction of allele-specific primers, without prior purification of the amplified sequences, and, finally, capture and visualization of the extension products within minutes on the device. Detection and monitoring are accomplished either by naked eye or by scanning with a common flatbed scanner. The total assay time is ∼ 2 h. The method was evaluated by using 21 clinical samples of known genotypes. The results were fully concordant with the reference method (sequencing). The proposed method is accurate, simple, rapid, and cost-effective. Visual detection does not require specialized instrumentation or highly trained technical personnel. We anticipate that the proposed device will become a useful analytical tool for precision medicine of breast cancer.