Clusterin/apolipoprotein J is associated with cortical Lewy bodies: immunohistochemical study in cases with alpha-synucleinopathies

Abstract

Clusterin/apolipoprotein J protein expression in cases with "alpha-synucleinopathies", such as Parkinson's disease (PD), dementia with Lewy bodies (DLB) and multiple system atrophy (MSA), was investigated using an immunohistochemical method for the labeling of multiple antigens. About 50% of the cortical Lewy bodies in the cases with DLB were immunoreactive for clusterin, whereas brain-stem Lewy bodies in PD and DLB were rarely associated with clusterin. Clusterin was also immunopositive in around 10% of the glial cytoplasmic inclusions (GCIs) in the cases with MSA. Colocalization of clusterin with alpha-synuclein in such bodies or inclusions was clearly correlated with the immunostaining pattern of alpha-synuclein. Subcellular localization of clusterin was almost completely overlapped with the homogeneous immunoreaction of alpha-synuclein in the cortical Lewy bodies; however, clusterin immunoreactivity was not detected in the halo or ring-like structures of the brain-stem Lewy bodies. Furthermore, some Lewy bodies with intense immunoreactivity for clusterin showed only a weak signal for alpha-synuclein. These results suggest that clusterin may modify the formation of alpha-synuclein-positive inclusion bodies such as Lewy bodies and GCIs, through a previously proposed chaperone property of clusterin.