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%. Specificity was 100%. 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.