Novel fluid biomarkers in synucleinopathies

A number of fluid biomarkers have recently been identified as diagnostic and prognostic markers in the field of synucleinopathies. These include catecholamines, neurofilament light chain (NfL), protein misfolding assays, as well as exosomal markers. Particularly the protein misfolding assays have shown great promise not only in the detection of synuclein pathology, but also in the differentiation of Lewy-body synucleinopathies from multiple system atrophy (MSA). Particularly when combined with NfL, these assays allow for faithful differentiation of MSA from Parkinson disease (PD) and dementia with Lewy bodies (DLB). This combination of biomarkers furthermore allows for prediction of future phenoconversion of pure autonomic failure to MSA. The elegant nature of the exosome approach paired with the convenience to derive exosomal markers from blood will undoubtedly lead to further work in this field, which will hopefully overcome the current methodological differences and conflicting results.