Ageing and Neurodegeneration, Neuroscience Research Australia, Randwick, Sydney, Australia; University of New South Wales, Sydney, Australia.
Ageing and Neurodegeneration, Neuroscience Research Australia, Randwick, Sydney, Australia; University of New South Wales, Sydney, Australia.
Neurobiol Aging. 2020 May;89:129-131. doi: 10.1016/j.neurobiolaging.2019.10.025. Epub 2019 Nov 8.
Clusterin (CLU) is a pleiotropic glycoprotein that exists as a secreted, neuroprotective or intracellular, neurotoxic form, both of which increase in Alzheimer's disease (AD) causing increased Aβ42 deposition. No studies have assessed the association between functionally distinct alloforms of CLU and tau protein or neuronal loss, despite its intracellular toxicity. We confirm previous reports of significant increases in both intracellular CLU and secreted CLU in the brain tissue of individuals with AD (p < 0.01) and show no association with neuronal loss. The increase in CLU alloforms was most closely associated with increases in both insoluble Aβ42 and tau protein (p = 0.001), supporting its role in AD pathogenesis. Further research should investigate whether altering human CLU levels may have viability as a therapeutic option for AD.
簇集蛋白（CLU）是一种多效糖蛋白，存在于分泌型、具有神经保护作用或细胞内型、具有神经毒性两种形式，这两种形式在阿尔茨海默病（AD）中都会增加，导致 Aβ42 沉积增加。尽管其具有细胞内毒性，但尚无研究评估 CLU 的功能不同同种型与tau 蛋白或神经元丢失之间的关联。我们证实了先前的报告，即在 AD 患者的脑组织中，细胞内 CLU 和分泌型 CLU 均显著增加（p < 0.01），并且与神经元丢失无关。CLU 同种型的增加与不溶性 Aβ42 和 tau 蛋白的增加最密切相关（p = 0.001），支持其在 AD 发病机制中的作用。进一步的研究应探讨是否改变人类 CLU 水平可能作为 AD 的治疗选择具有可行性。
