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. © 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.