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Monitoring conformational variants of a-synuclein (SNCA) to classify neurodegenerative diseases

Distinct conformational variants of SNCA could be useful as biomarkers for distinguishing between subtypes of neurodegenerative diseases including Parkinson's disease (PD). In cultured mouse neurons, expression of two different synthetic conformational variants of human SNCA drove distinct patterns of SNCA and microtubule-associated protein-t (MAPT; TAU; FTDP-17) inclusion formation. In brain tissue samples from five patients with PD and dementia, two showed expression of a single SNCA conformation, whereas the other three showed expression of two SNCA conformations. Next steps include studies to determine why different SNCA variants produce distinct disease pathologies and to understand the significance of such differences.

SciBX 6(30); doi:10.1038/scibx.2013.811
Published online Aug. 8, 2013

Patent application filed covering antibodies against the different SNCA variants; unavailable for licensing

Guo, J.L. et al. Cell;
published online July 3, 2013;
Contact: Virginia M.Y. Lee, University of Pennsylvania School of Medicine, Philadelphia, Pa.