Increased collagen content of cerebral microvessels in Alzheimer's disease
Increased collagen content of cerebral microvessels in Alzheimer's disease
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DOI：
10.1016/0006-8993(95)01250-8
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发表时间：
1995-12-24
期刊：
影响因子：
2.9
通讯作者：
Pax, AB
中科院分区：
文献类型：
--
作者：
Kalaria, RN;Pax, AB
基于先前的证据表明异常的大脑微血管，我们研究了基底膜胶原蛋白在分离的脑微血管（CMV）与阿尔茨海默病（AD）和年龄匹配的对照组。与对照组相比，来自AD受试者的CMV中IV型胶原的主要成分羟脯氨酸的浓度显著增加了55%。这一结果得到了CMV中总胶原含量增加60%的发现的证实，如天狼星红染料的选择性结合所证明的。平行测定的大脑皮层样品中的羟脯氨酸和胶原蛋白浓度比CMV小6-20倍，并且在对照组和AD受试者之间没有变化。为了进一步区分AD和对照样品，将CMV的级分溶解，并通过SDS-PAGE解析胃蛋白酶消化的胶原蛋白。免疫印迹后，AD样品与胶原蛋白增加显示成比例更高的特异性免疫反应检测到的抗体胶原蛋白IV。我们的观察结果表明，改变胶原IV含量的AD患者的脑血管，可能会影响脑微血管功能。
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.