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 mRN A 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 ab out 40% higher in AD than in controls. Purified clusterin from human b rain was slightly smaller than serum clusterin. Brain and serum cluste rin were indistinguishable in the inhibition of complement-mediated he molysis. Both serum and brain clusterin were indistinguishable in inhi biting the aggregation of A beta and promoting oxidative stress in rat pheochromocytoma PC12 cells (MTT assay). The inhibition of A beta agg regation and enhancement of A beta toxicity by clusterin suggest new m echanisms in AD. (C) 1994 Academic Press, Inc.