Despite the extensive studies into α-syn proteoforms in CSF, plasma/serum, brain tissue, appendix and saliva (Guerreiro et al., 2012; Kellie et al., 2014; Oeckl et al., 2016; Killinger et al., 2018; Bhattacharjee et al., 2019; Mollenhauer et al., 2019) it appears that total synuclein concentrations are global markers of synaptic degeneration rather than specific clinical diagnostics for synucleinopathies. This evidence concerns the gene SNCA and synucleinopathy.