The purpose of this analysis was to confirm prior findings showing high sensitivity and specificity for alpha-synuclein seed amplification from CSF in Parkinson’s disease, and to extend these findings to subgroups and prodromal individuals. We found that a-syn SAA accurate differentiates PD patients from healthy controls and from SWEDDS. Subgroups, particularly LRRRK2 PD, had lower rates of SAA positive results. We also found a high rate of SAA positive results in hyposmic and RBD cases, but not in asymptomatic gene carriers of LRRK2 or GBA. These results have implications for clinical trial planning in manifest PD and prodromal cases.