Purification and characterization of brain clusterin

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 β-amyloid (Aβ). These studies characterized clusterin protein from human brain. In extracts form 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 Aβ and promoting oxidative stress in rat pheochromocytoma PC12 cells (MTT assay). The inhibition of Aβ aggregation and enhancement of Aβ toxicity by clusterin suggest new mechanisms in AD.