Apolipoprotein J (clusterin) and Alzheimer's disease.
Apolipoprotein J (clusterin) is a ubiquitous multifunctional glycoprotein capable of interacting with a broad spectrum of molecules. In pathological conditions, it is an amyloid associated protein, co-localizing with fibrillar deposits in systemic and localized amyloid disorders. In Alzheimer's disease, the most frequent form of amyloidosis in humans and the major cause of dementia in the elderly, apoJ is present in amyloid plaques and cerebrovascular deposits but is rarely seen in NFT-containing neurons. ApoJ expression is up-regulated in a wide variety of insults and may represent a defense response against local damage to neurons. Four different mechanisms of action could be postulated to explain the role of apoJ as a neuroprotectant during cellular stress: (1) function as an anti-apoptotic signal, (2) protection 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 soluble Abeta. This interaction prevents Abeta aggregation and fibrillization and modulates its blood-brain barrier transport at the cerebrovascular endothelium.
Department of Pathology, New York University School of Medicine, New York 10016, USA.
M
M
Calero
A
A
Rostagno
E
E
Matsubara
B
B
Zlokovic
B
B
Frangione
J
J
Ghiso
D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000686:Amyloidosis / Q000378:metabolism; D001812:Blood-Brain Barrier; D001921:Brain / Q000098:blood supply / Q000378:metabolism / Q000473:pathology; D051152:Clusterin; D004730:Endothelium, Vascular / Q000378:metabolism / Q000473:pathology; D006023:Glycoproteins / Q000134:cerebrospinal fluid / Q000378:metabolism*; D006801:Humans; D018832:Molecular Chaperones; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D058225:Plaque, Amyloid / Q000378:metabolism
D016229:Amyloid beta-Peptides; C495242:CLU protein, human; D051152:Clusterin; D006023:Glycoproteins; D018832:Molecular Chaperones; D009419:Nerve Tissue Proteins