Dementia Research Group, Institute of Clinical Neurosciences, School of Clinical Sciences, University of Bristol, Bristol, UK.
Neurobiol Aging. 2012 Jul;33(7):1345-55. doi: 10.1016/j.neurobiolaging.2010.09.024. Epub 2010 Nov 11.
Decreased cerebral blood flow and blood-brain barrier disruption are features of Alzheimer's disease (AD). The plasma kallikrein-kinin system modulates cerebrovascular tone through release of vasoactive bradykinin (BK). Cerebroventricular infusion of Aβ1-40 enhances BK release, suggesting that the activity of this system may be elevated in AD. We investigated the profile of the activating protease of this system, plasma kallikrein (PK), in frontal and temporal brain tissue from postmortem confirmed cases of AD, vascular dementia (VaD), and controls. Measurements of neuron specific enolase messenger ribonucleic acid (mRNA) and protein were used to adjust for neuronal loss. Adjusted PK mRNA was significantly increased in the frontal cortex in AD, and the frontal and temporal cortex in VaD. Similar trends were seen for PK protein level in AD and VaD. PK activity was significantly increased in the frontal and temporal cortex in AD. Increased PK activity in AD is likely to contribute to increased BK release and may thereby influence cerebral blood flow and vascular permeability.
脑血流量减少和血脑屏障破坏是阿尔茨海默病（AD）的特征。血浆激肽释放酶-激肽系统通过释放血管活性缓激肽（BK）来调节脑血管张力。脑室内输注 Aβ1-40 可增强 BK 的释放，提示该系统的活性在 AD 中可能升高。我们研究了 AD、血管性痴呆（VaD）和对照患者死后确认的额颞叶脑组织中该系统的激活蛋白酶，即血浆激肽释放酶（PK）的特征。使用神经元特异性烯醇化酶信使核糖核酸（mRNA）和蛋白的测量值来调整神经元丢失。AD 患者的额皮质中调整后的 PK mRNA 显著增加，VaD 患者的额皮质和颞皮质中也有类似的趋势。AD 和 VaD 患者的 PK 蛋白水平也有类似的趋势。AD 患者的额皮质和颞皮质中 PK 活性显著增加。AD 中 PK 活性的增加可能导致 BK 释放增加，从而影响脑血流量和血管通透性。
