In situ and in vitro study of colocalization and segregation of α-synuclein, ubiquitin, and lipids in Lewy bodies

alpha -Synuclein and ubiquitin are two Lewy body protein components that may play antagonistic roles in the pathogenesis of Lewy bodies. We examined the relationship between alpha -synuclein, ubiquitin, and lipids in Lewy bodies of fixed brain sections or isolated from cortical tissues of dementia with Lewy bodies. Lewy bodies exhibited a range of labeling patterns for alpha -synuclein and ubiquitin, from a homogeneous pattern in which alpha -synuclein and ubiquitin were evenly distributed and overlapped across the inclusion body to a concentric pattern in which alpha -synuclein and ubiquitin were partially segregated, with alpha -synuclein labeling concentrated in the peripheral domain and ubiquitin in the central domain of the Lewy body. Lipids represented a significant component in both homogeneous and concentric Lewy bodies. These results suggest that Lewy bodies are heterogeneous in their subregional composition. The segregation of alpha -synuclein to Lewy body peripheral domain is consistent with the hypothesis that alpha -synuclein is continually deposited onto Lewy bodies. (C) 2000 Academic Press.