Zhao Zhong, Xiang Zhongmin, Haroutunian Vahram, Buxbaum Joseph D, Stetka Breton, Pasinetti Giulio Maria
Neuroinflammation Research Laboratories, The Mount Sinai School of Medicine, New York, NY 10029, United States.
Neurobiol Aging. 2007 Jun;28(6):824-30. doi: 10.1016/j.neurobiolaging.2006.05.001. Epub 2006 Jun 12.
In this study we report that the membrane-bound, but not cytosolic insulin degrading enzyme (IDE) protein concentration and IDE activity are significantly decreased in the hippocampal formation of cases affected by mild cognitive impairment (MCI) which are at high risk to develop Alzheimer's disease (AD), relative to normal neurological controls. Membrane-bound IDE protein concentrations and activity in the hippocampal formation continued to decrease during the conversion from MCI to mild-severe AD. This selective decrease in hippocampal membrane-bound, but not cytosolic, IDE concentration and activity was tissue specific since no changes in either membrane-bound or cytosolic IDE were found in the occipital cortex of the same cases examined. Most interestingly, the decreased hippocampal membrane-bound IDE protein activity negatively correlated with brain beta-amyloid (Abeta)X-42 content in MCI and in AD brain. The study tentatively suggests that interventions aimed at promoting membrane-bound IDE activities in the brain of MCI cases may help to prevent the onset and possibly the progression into AD through mechanisms involving the clearance of monomeric Abeta from the brain.
在本研究中，我们报告称，与正常神经对照组相比，在有发展为阿尔茨海默病（AD）高风险的轻度认知障碍（MCI）患者的海马结构中，膜结合型而非胞质型胰岛素降解酶（IDE）的蛋白浓度和IDE活性显著降低。在从MCI转变为轻度至重度AD的过程中，海马结构中膜结合型IDE的蛋白浓度和活性持续下降。海马膜结合型而非胞质型IDE浓度和活性的这种选择性降低具有组织特异性，因为在检查的相同病例的枕叶皮质中，膜结合型或胞质型IDE均未发现变化。最有趣的是，海马膜结合型IDE蛋白活性的降低与MCI和AD脑中的脑β-淀粉样蛋白（Aβ）X-42含量呈负相关。该研究初步表明，旨在促进MCI患者脑中膜结合型IDE活性的干预措施可能有助于通过涉及从脑中清除单体Aβ的机制来预防AD的发作，并可能预防其进展。
