Strong Predictive Algorithm of Pathogenesis-Based Biomarkers Improves Parkinson's Disease Diagnosis

Easily accessible and accurate biomarkers can aid Parkinson's disease diagnosis. We investigated whether combining plasma levels of alpha-synuclein, anti-alpha-synuclein, and/or their ratios to amyloid beta-40 correlated with clinical diagnosis. The inclusion of amyloid beta-40 (A beta 40) is novel. Plasma levels of biomarkers were quantified with ELISA. Using receiver operating characteristic (ROC) curve analysis, levels of alpha-synuclein, anti-alpha-synuclein, and their ratios with A beta 40 were analyzed in an initial training set of cases and controls. Promising biomarkers were then used to build a diagnostic algorithm. Verification of the results of biomarkers and the algorithm was performed in an independent set. The training set consisted of 50 cases (age 65.2 +/- 9.3, range 44-83, female:male=21:29) with 50 age- and gender-matched controls (67.1 +/- 10.0, range 45-96 years; female:male=21:29). ROC curve analysis yielded the following area under the curve results: anti-alpha-synuclein=0.835, alpha-synuclein=0.738, anti-alpha-synuclein/A beta 40=0.737, and alpha-synuclein/A beta 40=0.663. A 2-step diagnostic algorithm was built: either alpha-synuclein or anti-alpha-synuclein was >= 2 times the means of controls (step-1), resulting in 74% sensitivity; and adding alpha-synuclein/A beta 40 or anti-alpha-synuclein/A beta 40 (step-2) yielded better sensitivity (82%) while using step-2 alone yielded good specificity in controls (98%). The results were verified in an independent sample of 46 cases and 126 controls, with sensitivity reaching 91.3% and specificity 90.5%. The algorithm was equally sensitive in Parkinson's disease of <= 5-year duration with 92.6% correctly identified in the training set and 90% in the verification set. With two independent samples totaling 272 subjects, our study showed that combination of biomarkers of alpha-synuclein, anti-alpha-synuclein, and their ratios to A beta 40 showed promising sensitivity and specificity.

Automated summary

This study investigated the correlation between plasma levels of alpha-synuclein, anti-alpha-synuclein, and their ratios to amyloid beta-40 in Parkinson's disease diagnosis. A diagnostic algorithm was built using promising biomarkers, and the results were verified in an independent sample. The study showed that the combination of these biomarkers demonstrated promising sensitivity and specificity.