Plasma α-syn showed 80% sensitivity and 93.9% specificity with an AUC of 0.889 for differentiating PDSs (PD, MSA, and PSP) from HC, with the highest diagnostic value among individual biomarkers, whereas a combination of Aβ42, Aβ40, Aβ42/40, NfL, and α-syn could achieve a better diagnostic value in differentiating PDSs from HC with an AUC of 0.983 with 98.5% sensitivity and 93.9% specificity. This evidence concerns the gene NEFL and multiple system atrophy.