Clusterin as a biomarker for Alzheimer’s disease

Objective. To examine and systematically review the existing literature regarding clusterin (CLU) as a potential biomarker for Alzheimer’s disease. Material and methods. A comprehensive analysis of data, including generalization, comparison, and systematization, was conducted to review findings from both Russian and international publications. The study included a thorough search of the PubMed (MEDLINE) database and other scientific information sources over the last decade. The collected data underwent analytical scrutiny to elucidate the potential significance of CLU in AD pathogenesis. Results. This article presents evidence indicating that clusterin (CLU) may play a significant role in AD pathogenesis through various mechanisms, including regulation of inflammation, modulation of cellular apoptosis, facilitation of clearance of pathological proteins, and affecting oxidative stress and the aggregation and folding of extracellular proteins. CLU plays a vital role in promoting cell survival under stressful conditions. It offers protection against oxidative stress, ensuring both immediate resistance to damage and prolonged cellular viability. A loss of soluble clusterin (sCLU) protective function in response to ROS-induced damage may render neurons more susceptible to additional insults, such as Aβ, which generates H2O2 and other reactive oxygen species. Furthermore, CLU can activate the PI3K/Akt signaling pathway, which functions as an effector of mTOR and NF-κB. Inhibition of mTOR has been associated with a slowing of AD progression. Notably, elevated plasma levels of CLU in healthy older adults may precede significant Aβ deposition in the brain by as much as ten years, suggesting an early elevation of CLU within the pathogenesis of AD and its potential pathological implications. Conclusions. Clusterin should be considered a significant biomarker for Alzheimer’s disease, supporting the use of enzyme-linked immunosorbent assays to measure plasma CLU concentrations. This approach may serve as an additional tool for early screening and therapeutic interventions in Alzheimer’s disease.