Salivary total α-synuclein, oligomeric α-synuclein and SNCA variants in Parkinson’s disease patients

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.

Salivary Biomarkers for Alzheimer’s Disease and Related Disorders

“…Yet, both increases and decreases in salivary total a-syn have been reported [72][73][74]. On the other hand, increases in oligomeric asyn [75] and oligomeric a-syn/total a-syn ratio have been demonstrated to be specific for PD [74,76]. To date, there has been no investigation of salivary a-syn in AD.…”

Salivary microR‐153 and microR‐223 Levels as Potential Diagnostic Biomarkers of Idiopathic Parkinson's Disease

“…Saliva has advantages over other biofluids and imaging techniques because its acquisition is noninvasive, inexpensive, and requires minimal personnel training . Most groups report reduced salivary total α‐synuclein levels and higher oligomeric α‐synuclein levels in PD patients when compared with controls in addition to higher oligomeric to total α‐synuclein ratios …”

“…10,11 Most groups report reduced salivary total α-synuclein levels and higher oligomeric α-synuclein levels in PD patients when compared with controls in addition to higher oligomeric to total α-synuclein ratios. [12][13][14][15][16] In 2018, we reported increased concentrations of salivary heme oxygenase-1 (HO-1) in early-stage PD patients when compared with non-neurological controls. 17 HO-1 catalyzes the degradation of heme to biliverdin (further catabolized to bilirubin), free ferrous iron, and carbon monoxide.…”

Parkinson’s disease biomarkers based on α‐synuclein

“…However, these differences did not reach statistical significance, suggesting that t-a-syn would not suffice as a single biomarker in saliva. Other studies have focused on evaluating o-a-syn, reporting a marked increase in PD patients compared to healthy controls (Kang et al 2016), suggesting that the oligomeric form may have a greater potential for a disease biomarker (Kang et al 2016;Vivacqua et al 2016;Vivacqua et al 2019). This was further supported when o-asyn was evaluated in PD patients at different Hoehn & Yahr (H&Y) stages of the disease and reported significant increases with advancing disease stages.…”

“…Besides blood and CSF, α‐syn has also been explored to a lesser extent in other biofluids, such as saliva. Two studies reported reduced levels of saliva t‐α‐syn in PD compared to healthy controls (Devic et al ; Kang et al ), as well as lower levels of saliva t‐α‐syn in older patients (Kang et al 2016) . However, these differences did not reach statistical significance, suggesting that t‐a‐syn would not suffice as a single biomarker in saliva.…”