Skin α-synuclein seed amplification assay for the identification of multiple system atrophy

The α-synuclein seed amplification assay (synSAA) is a biomarker test that identifies underlying synuclein pathology in living patients. Cerebrospinal fluid (CSF) synSAA distinguishes Type 2 synuclein-seeds (syn-seeds) found in multiple system atrophy (MSA) from Type 1 syn-seeds found in other synucleinopathies. Skin has been proposed as an alternative biospecimen for synSAA, but syn-seeds have not been consistently detected and identified in MSA.

Here, we report a skin_synSAA for the detection of syn-seeds across synucleinopathies. The 126-participant cohort was enriched in Parkinson’s disease (PD, n = 64) and MSA (n = 28) cases. Skin_synSAA reached 69% and 75% sensitivities for PD and MSA.

Agreement with CSF_synSAA reached 84.3%. Amplification pattern of MSA skin samples allowed clear identification of Type 2 syn-seeds. Remarkably, there was 97.8% agreement in syn-seed type between skin and CSF.

Syn-seeds detected in skin correlated with those in CSF and allowed detection and differentiation of underlying synuclein pathology by means of skin_synSAA. We thank the participants and their families for their generous specimen donations supporting this research. We thank Sandra Rosete-Gonzalez for technical and lab management assistance.

We are deeply grateful for the work of Dr. Sebastian Schade, who contributed substantially to this study with data collection and brilliant clinical insights. His passion for advancing knowledge in Parkinson's disease and his commitment to this research will be deeply remembered, and we are honored to have had the privilege of working with him.

This research was partially funded by Amprion, the University Medical Center Gottingen through UMG Clinic Scientist Program to Dr. Sandrina Weber, and the Michael J. Fox Foundation for Parkinson’s Research (MJFF) through grant MJFF-024735 to Dr.