A minimally invasive biomarker for sensitive and accurate diagnosis of Parkinson's disease

Seeding activities of disease-associated alpha-synuclein aggregates (alpha Syn(D)), a hallmark of Parkinson's disease (PD), are detectable by seed amplification assay (alpha Syn-SAA) and being developed as a diagnostic biomarker for PD. Sensitive and accurate alpha Syn-SAA for blood or saliva would greatly facilitate PD diagnosis. This prospective diagnostic study conducted alpha Syn-SAA analyses on serum and saliva samples collected from patients clinically diagnosed with PD or healthy controls (HC). 124 subjects (82 PD, 42 HC) donated blood and had extensive clinical assessments, of whom 74 subjects (48 PD, 26 HC) also donated saliva at the same visits. An additional 57 subjects (35 PD, 22 HC) donated saliva and had more limited clinical assessments. The mean ages were 69.21, 66.55, 69.58, and 64.71 years for PD serum donors, HC serum donors, PD saliva donors, and HC saliva donors, respectively. alpha Syn(D) seeding activities in either sample type alone or both sample types together were evaluated for PD diagnosis. Serum alpha Syn-SAA data from 124 subjects showed 80.49% sensitivity, 90.48% specificity, and 0.9006 accuracy (AUC of ROC); saliva alpha Syn-SAA data from 131 subjects attained 74.70% sensitivity, 97.92% specificity, and 0.8966 accuracy. Remarkably, the combined serum and saliva alpha Syn-SAA from 74 subjects with both sample types achieved better diagnostic performance: 95.83% sensitivity, 96.15% specificity, and 0.98 accuracy. In addition, serum alpha Syn(D) seeding activities correlated inversely with Montreal Cognitive Assessment in males and positively with Hamilton Depression Rating Scale in females and in the < 70 age group, whereas saliva alpha Syn(D) seeding activities correlated inversely with age at diagnosis in males and in the < 70 age group. Our data indicate that serum and saliva alpha Syn-SAA together can achieve high diagnostic accuracy for PD comparable to that of CSF alpha Syn-SAA, suggesting their potential utility for highly sensitive, accurate, and minimally invasive diagnosis of PD in routine clinical practice and clinical studies.