Objective: To establish α-synuclein seeding activity in saliva as a noninvasive diagnostic biomarker for Parkinson’s disease (PD).

Background: PD is the second most common neurodegenerative disease, but accurate clinical diagnosis remains a challenge and a definitive diagnosis still relies on postmortem detection of neuronal inclusions of misfolded and aggregated alpha-synuclein protein (αSyn) in autopsy brain tissues. Deposition of disease-associated αSyn aggregates (αSyn^D) in the central nervous system is the pathological hallmark of PD and other synucleinopathies.  The recently developed αSyn-seeding activity assay (αSyn-SAA) can detect αSyn^D at high sensitivity and specificity utilizing the ultrasensitive real-time quaking induced conversion (RT-QuIC) assay. αSyn-SAA with cerebral spinal fluid (CSF) and biopsy skin have shown impressive sensitivity for PD and specificity for healthy controls (HC), but the invasive sampling procedures significantly impede patient acceptance and routine clinical application. A sensitive and reliable noninvasive biomarker would greatly facilitate PD diagnosis.

Method: Saliva samples were collected from 75 PD and 40 HC subjects and stored immediately at -80^oC before testing. The PD patients were subjected to extensive clinical assessments, including MDS-UPDRS motor score & modified Hoehn & Yahr (mH&Y). The mean age is 69.4±9.1 year (range: 46 to 87) or 65.1±9.9 years (range: 30 to 78) for PD and HC, respectively. The mean mH&Y score is 2.09±0.57 (range:1.0 to 4.0) for PD patients. The saliva samples were subjected to immunoprecipitation to enrich for soluble αSyn aggregates, followed by αSyn-SAA under optimized RT-QuIC conditions. An optimal cutoff value was set based on ROC analysis of the RT-QuIC data of the saliva samples from PD and HC. The diagnostic sensitivity and specificity were also calculated from the ROC curve.

Results: Our saliva αSyn-SAA data shows 70.7% sensitivity for PD, 92.5% specificity for HC, and a diagnostic accuracy of 0.866 (AUC of the ROC curve) (95% CI: 0.803-0.930) for PD (p<0.0001), which are similar to those in an earlier report.

Conclusion: Our data indicate that saliva αSyn-SAA can be developed as a noninvasive diagnostic biomarker for PD.  Further optimization of the saliva αSyn-SAA protocol might lead to a diagnostic accuracy rivaling those of CSF or skin αSyn-SAA.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/establishing-%ce%b1-synuclein-seeding-activity-in-saliva-as-a-noninvasive-diagnostic-biomarker-for-parkinsons-disease/