Kalaria R N, Pax A B
Department of Neurology, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA.
Brain Res. 1995 Dec 24;705(1-2):349-52. doi: 10.1016/0006-8993(95)01250-8.
Based on previous evidence suggesting abnormalities in the brain microvasculature, we examined basement membrane collagen in isolated cerebral microvessels (CMV) from subjects with Alzheimer's disease (AD) and age-matched controls. Concentrations of hydroxyproline, the principal constituent of collagen IV, were significantly increased by 55% in CMV from AD subjects compared to controls. This result was corroborated by the finding of 60% increased total collagen content in CMV as evident by the selective binding of Sirius red dye. Hydroxyproline and collagen concentrations in samples of cerebral cortex assayed in parallel were 6-20 times smaller than in CMV and were not changed between controls and AD subjects. To further differentiate AD and control samples, fractions of CMV were solubilized and the pepsin digested collagen proteins resolved by SDS-PAGE. Upon immunoblotting, AD samples with increased collagen revealed proportionally greater specific immunoreactivities detected by antibodies to collagen IV. Our observations suggest altered collagen IV content of cerebral vessels in subjects with AD that may affect brain microvascular functions.
基于先前表明脑微血管存在异常的证据，我们检测了来自阿尔茨海默病（AD）患者及年龄匹配对照组的分离脑微血管（CMV）中的基底膜胶原蛋白。与对照组相比，AD患者CMV中胶原蛋白IV的主要成分羟脯氨酸浓度显著增加了55%。天狼星红染料的选择性结合表明，CMV中总胶原蛋白含量增加60%，这一结果证实了上述发现。同时检测的大脑皮质样本中的羟脯氨酸和胶原蛋白浓度比CMV中的低6 - 20倍，且在对照组和AD患者之间没有变化。为了进一步区分AD和对照样本，将CMV组分溶解，用胃蛋白酶消化胶原蛋白蛋白，通过SDS - PAGE分离。免疫印迹后，胶原蛋白增加的AD样本显示，针对胶原蛋白IV的抗体检测到的特异性免疫反应性成比例增加。我们的观察结果表明，AD患者脑血管中胶原蛋白IV含量改变，这可能会影响脑微血管功能。
