The histological hallmark of Parkinson's disease (PD) is the presence of fibrillar aggregates called Lewy bodies (LBs). LB formation has been considered to be a marker for neuronal degeneration, because neuronal loss is found in the predilection sites for LBs. To date, more than 70 molecules have been identified in LBs, in which α-synuclein is a major constituent of LB fibrils. α-synuclein immunohistochemistry reveals that diffuse cytoplasmic staining develops into pale bodies via compaction, and that LBs arise from the peripheral portion of pale bodies. This α-synuclein abnormality is found in 10% of pigmented neurons in the substantia nigra and more than 50% of those in the locus ceruleus in PD. Recent studies have suggested that oligomers and protofibrils of α-synuclein are cytotoxic, and that LBs may represent a cytoprotective mechanism in PD.