Purification and characterization of brain clusterin

Abstract

Clusterin, a 70-80 kDa sulfated glycoprotein found in numerous tissues, is also known as complement lysis inhibitor (CLI), apolipoprotein J, SP-40,40, TRPM-2, and SGP-2. In Alzheimer disease (AD), clusterin mRNA is increased, whereas clusterin protein is found in deposits of beta-amyloid (A beta). These studies characterized clusterin protein from human brain. In extracts from cortex and hippocampus, clusterin was about 40% higher in AD than in controls. Purified clusterin from human brain was slightly smaller than serum clusterin. Brain and serum clusterin were indistinguishable in the inhibition of complement-mediated hemolysis. Both serum and brain clusterin were indistinguishable in inhibiting the aggregation of A beta and promoting oxidative stress in rat pheochromocytoma PC12 cells (MTT assay). The inhibition of A beta aggregation and enhancement of A beta toxicity by clusterin suggest new mechanisms in AD.