β-Amyloid Upregulates Intracellular Clusterin but not Secretory Clusterin in Primary Cultured Neurons and APP Mice

Background: Previous studies have suggested that the expression of Aβ and clusterin is positively correlated. However, the causal relationship between Aβ and clusterin has not been exactly clarified. Methods: In this study, primary hippocampal neurons were treated with Aβ42; clusterin mRNA and protein expression was assessed. Furthermore, we evaluated Aβ and clusterin protein expression in the brains of APP/PSEN1 mice, as well as serum clusterin concentration. Results: We observed here that the exposure of primary hippocampal neurons to Aβ42 induced an overexpression of intracellular clusterin, but the level of clusterin in supernatants was not changed. Moreover, in APP/PSEN1 mice, there was a significant increase in intracellular clusterin in cortex and hippocampus, compared to age-matched WT mice, while serum clusterin level in APP/PSEN1 mice and in WT mice has no significant difference. Conclusion: Aβ42 upregulated intracellular clusterin, but secretory clusterin did not change. These findings reveal that clusterin is upregulated by Aβ and is responsive to AD pathology, although plasma clusterin concentration is not evidenced to be a stand-alone biomarker for AD. Keywords: Clusterin, β-amyloid, Alzheimer's disease, upregulation, intracellular clusterin, secretory clusterin.