A panel of epitope-specific antibodies detects protein domains distributedthroughout human alpha-synuclein in Lewy bodies of Parkinson's disease

To facilitate studies of the normal biology of alpha-synuclein, a member of a family of neuronal proteins of unknown function, and to elucidate the ro le of alpha-synuclein pathologies in neurodegenerative diseases, we generat ed and characterized a panel of anti-synuclein antibodies. Mere we demonstr ate that these antibodies recognize defined epitopes spanning the entire le ngth of human alpha-synuclein, and that some of these antibodies also cross -react with zebra finch and rodent synucleins. Since alpha-synuclein has be en reported to be a major component of Lewy bodies (LBs) in Parkinson's dis ease (PD), dementia with LBs and common variants of Alzheimer's disease, we performed immunohistochemical studies showing that these antibodies label numerous LBs in the PD substantia nigra, thereby localizing protein domains throughout human alpha-synuclein in LBs. Taken together, our data indicate that this panel of antibodies can be exploited to probe the normal biology of alpha-synuclein as well as the role of pathological forms of this prote in in PD and related neurodegenerative synucleinopathies. (C) 2000 Wiley-Li ss, Inc.