Alpha-synuclein (SNCA), with 140-amino acid protein (about 15kDa), belongs to the synuclein family, which also includes beta- and gamma-synuclein. SNCA is a soluble protein, expressed principally in the brain but also expressed in low concentrations in all tissues examined (except liver). SNCA is implicated in the regulation of dopamine release and transport. The triplication of the SNCA can cause Parkinson disease (PD) and diffuse Lewy body disease within the same kindred. SNCA peptides are a major component of amyloid plaques in the brains of patients with Alzheimer’s disease. Immunohistochemistry for SNCA has become the histological technique of choice for the diagnosis for Parkinson’s disease, Dementia with Lewy bodies and Multiple System Atrophy.