Differential expression of α-synuclein isoforms in dementia with Lewy bodies

Dementia with Lewy bodies (DLB) is characterized by the widespread presence of Lewy bodies (LBs) in the brain. α-Synuclein, the main component of LBs, is expressed as two main isoforms (112 and 140), but little is known about their differential expression in the brain. We compared α-synuclein 112 and α-synuclein 140 expression levels in the prefrontal cortices of six DLB patients, eight Alzheimer disease (AD) patients, and six control subjects. Relative α-synuclein 112 and α-synuclein 140 expression levels were determined by real-time polymerase chain reaction with competimer technology using a LightCycler System. Whereas total α-synuclein levels were just marginally elevated in DLB in comparison with the other groups, α-synuclein 112 was seen to be markedly increased in DLB compared with AD cases and controls. In contrast, α-synuclein 140 levels were significantly diminished in both neurodegenerative disorders in comparison with controls. These results show differential overexpression of α-synuclein 112 in DLB, a finding that could be of importance in DLB pathogenesis.