Comparison of Two α‐Synuclein Seed Amplification Assays for Discrimination of Parkinson Disease and Atypical Parkinsonism

Background Seed amplification assays (SAAs) for misfolded α‐synuclein (syn) have shown inconsistent results in multiple system atrophy (MSA). Objective The objective of this study was to compare a novel syn SAA (synSAA) that distinguishes between Lewy body disease (LBD) and MSA syn‐seeds (Amprion‐SAA) with an LBD‐specific synSAA (IRCCS Istituto delle Scienze Neurologiche di Bologna [ISNB]‐SAA). Methods We applied both assays to cerebrospinal fluid samples from 114 patients with MSA, 49 patients with Parkinson disease (PD), 40 patients with progressive supranuclear palsy (PSP), and 46 controls. Results Amprion‐SAA detected type 2 (“MSA‐type”) syn‐seeds in 101 (88.6%) MSA, 3 (6.1%) PD, 4 (10.0%) PSP, and 6 (13.0%) control participants, and type 1 (“LBD‐type”) syn‐seeds in 39 (79.6%) PD, 3 (2.6%) MSA, and 1 (2.5%) PSP participant. ISNB‐SAA detected LBD‐specific syn‐seeds in 40 (81.6%) PD, 4 (3.5%) MSA, and none of the PSP or control participants. Conclusions Amprion‐SAA, performed at ISNB, uniquely discriminated MSA from both PD and PSP participants with good accuracy. However, it showed lower specificity than ISNB‐SAA, primarily related to the type 2 profile.