Synucleinopathies are a spectrum of neurodegenerative diseases characterized by 
the intracellular deposition of the protein α-synuclein leading to multiple 
outcomes, including dementia and Parkinsonism. Recent findings support the 
notion that across the spectrum of synucleinopathies there exist diverse but 
specific biochemical modifications and/or structural conformations of 
α-synuclein, which would give rise to protein strain specific prion-like 
intercellular transmission, a proposed model that could explain 
synucleinopathies disease progression. Herein, we characterized a panel of 
antibodies with epitopes within both the C- and N- termini of α-synuclein. A 
comprehensive analysis of human pathological tissue and mouse models of 
synucleinopathy with these antibodies support the notion that α-synuclein exists 
in distinct modified forms and/or structural variants. Furthermore, these 
well-characterized and specific tools allow the investigation of biochemical 
changes associated with α-synuclein inclusion formation. We have identified 
several antibodies of interest with diverse staining and epitope properties that 
will prove useful in future investigations of strain specific disease 
progression and the development of targeted immunotherapeutic approaches to 
synucleinopathies.