Exploring the Role ofCLUin the Pathogenesis of Alzheimer's Disease

Alzheimer's disease (AD) is a chronic and devastating neurodegenerative disorder that is affecting elderly people at an increasing rate. Clusterin (CLU), an extracellular chaperone, is an ubiquitously expressed protein that can be identified in various body fluids and tissues. Expression ofCLUcan lead to various processes including suppression of complement system, lipid transport, chaperone function, and also controlling neuronal cell death and cell survival mechanisms. Studies have confirmed that the level ofCLUexpression is increased in AD. Furthermore, CLU also decreased the toxicity and aggregation of amyloid beta (A beta). However when the A beta level was far greater than CLU, then the amyloid generation was increased. CLU was also found to incorporate in the amyloid aggregates, which were more harmful as compared with the A beta 42 aggregates alone. Growing evidence indicates that CLU plays roles in AD pathogenesis via various processes, including aggregation and clearance of A beta, neuroinflammation, lipid metabolism, Wnt signaling, copper homeostasis, and regulation of neuronal cell cycle and apoptosis. In this article, we represent the critical interaction of CLU and AD based on recent advances. Furthermore, we have also focused on the A beta-dependent and A beta-independent mechanisms by which CLU plays a role in AD pathogenesis.