Department of Neurology, Changzheng Hospital, Second Military Medical University, Shanghai, China

*These authors contributed equally to this work.

Abstract 

Alzheimer’s disease (AD) remains a major killer, and although its pathogenesis varies, one dominant feature is an increase in the expression, formation, and sedimentation of senile plaques of amyloid-beta (Aβ) peptides in the brain. The chaperone protein clusterin has, since its fi rst discovery at the end of the 20th century, been labeled as a cytoprotector. However, epigenetic studies showing that clusterin is associated with the severity and risk of AD, especially in the hippocampus, triggered studies to clarify its role in the pathogenesis of AD. It is true that clusterin can inhibit the aggregation of Aβ and therefore prevent further formation of senile plaques in the AD brain, yet it induces the formation of soluble forms of Aβ which are toxic to neurons. Another problematic fi nding is that clusterin is involved in a pathway through which Aβ has neurodegenerative effects intracellularly. Although the role of clusterin in the pathogenesis of AD is still not clear, this review specifi cally discusses the interactions between clusterin and Aβ, to open up the possibility of a potential therapeutic approach for treating AD.

Keywords

clusterin; Alzheimer’s disease; amyloid-beta peptides; cytotoxicity; cytoprotection

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