Apolipoprotein J (clusterin) and Alzheimer's disease

Apolipoprotein J (clusterin) is a ubiquitous multifunctional glycoprotein c apable of interacting with a broad spectrum of molecules. In pathological c onditions, it is an amyloid associated protein, co-localizing with fibrilla r deposits in systemic and localized amyloid disorders. In Alzheimer's dise ase, the most frequent form of amyloidosis in humans and the major cause of dementia in the elderly, apoJ is present in amyloid plaques and cerebrovas cular deposits but is rarely seen in NFT-containing neurons. ApoJ expressio n is up-regulated in a wide variety of insults and may represent a defense response against local damage to neurons. Four different mechanisms of acti on could be postulated to explain the role of apoJ as a neuroprotectant dur ing cellular stress: (1) function as an anti-apoptotic signal, (2) protecti on against oxidative stress, (3) inhibition of the membrane attack complex of complement proteins locally activated as a result of inflammation, and ( 4) binding to hydrophobic regions of partially unfolded, stressed proteins, and therefore avoiding aggregation in a chaperone-like manner. This review focuses on the association of apoJ in biological fluids with Alzheimer's s oluble AP. This interaction prevents Ap aggregation and fibrillization and modulates its blood-brain barrier transport at the cerebrovascular endothel ium. (C) 2000 Wiley-Liss, Inc.