Abstract
The present study was to evaluate the diagnostic value of salivary total and oligomeric α-synuclein levels in PD. Furthermore, we sought to explore the relationship between salivary total α-synuclein and α-synuclein SNP variants levels. 201 PD patients and 67 controls were recruited, of which there also had the genetic information of two positive α-synuclein (SNCA) loci. Salivary total α-synuclein was assayed using a highly sensitive Luminex assay and oligomeric α-synuclein was quantified by the combination of Gel filtration chromatography and Western blot, respectively. From our analysis,No difference in salivary total α-synuclein levels was found between PD patients and healthy controls, it decreased with age in PD patients, and was closely associated with genotypic distribution of rs11931074 and rs894278 in PD, respectively. After controlled for age and genders, G allele of rs11931074 was correlated with lower salivary total α-synuclein levels, while G allele of rs894278 was also correlated with the higher levels. Simultaneously, the further study was shown that salivary oligomeric α-synuclein in PD patients significantly increased comparing to healthy controls. In conclusions,our study firstly demonstrated that salivary total α-synuclein levels could be manipulated by different α-synuclein SNPs and salivary oligomeric α-synuclein could be a potential diagnostic indicator of PD.
Highlights
Parkinson’s disease (PD), the second most common neurodegenerative disease, is difficult to diagnose earlier due to its insidious onset
For further investigating the characteristics of salivary total α-synuclein in different groups, bivariate correlation analysis revealed that salivary α-synuclein levels decreased with age in PD patients (r =−0.162, p = 0.021; r =−0.211, p = 0.003 when normalized, Fig. 1B), but not in healthy controls (p = 0.32, p = 0.74 when normalized, Fig. 1B)
The present study demonstrated that: (1) Besides characterization of the nature of α-synuclein levels in saliva from PD patients, no difference of total salivary α-synuclein levels was found between PD and healthy controls
Summary
Parkinson’s disease (PD), the second most common neurodegenerative disease, is difficult to diagnose earlier due to its insidious onset. Some studies reported that CSF and plasma samples from patients with PD contain high levels of α-synuclein oligomers[5,6] and the RBC α-synuclein oligomer/total protein ratio can be a potential diagnostic biomarker for PD7. In our early study utilizing a small sample size, salivary α-synuclein seems to be a novel potential biomarker for PD4. The levels of salivary α-synuclein might be dependent on disease status but might be modified by genetic variability, i.e., in the α-synuclein (SNCA) gene itself. Altered expression of α-synuclein is considered one of the potential mechanisms contributing to the association between SNCA variants and PD development, indicating the possible correlation between genetic and biological markers. Whether a correlation exists between common risk-associated SNCA polymorphisms and peripheral α-synuclein levels such as saliva is not yet known
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