Zlokovic B V, Ghiso J, Mackic J B, McComb J G, Weiss M H, Frangione B
Department of Neurological Surgery, Childrens Hospital, Los Angeles, USC School of Medicine 90033.
Biochem Biophys Res Commun. 1993 Dec 30;197(3):1034-40. doi: 10.1006/bbrc.1993.2582.
The origin of amyloid beta (A beta) deposited in brain and cerebral blood vessels of patients with Alzheimer's Disease (AD) is not known. In this study, we tested whether soluble A beta (sA beta) can cross the blood-brain barrier (BBB). An in vivo vascular brain perfusion model and capillary depletion technique in guinea-pigs were used to determine cerebral capillary sequestration and blood-brain transport of a synthetic peptide identical with residues 1-40 (SP-40) of A beta. A saturable, specific binding of SP-40 has been demonstrated at the luminal side of the BBB, with the Kd of 25 +/- 2 nM, and Bmax of 188 +/- 11 fmol/min/g of isolated microvessels. A specific transcellular BBB transport of SP-40 into brain parenchyma exhibited the Km of 49 +/- 10 nM, and Vmax of 111 +/- 19 fmol/min/g of capillary depleted brain. We concluded that the BBB has the capability to control the cerebrovascular sequestration and blood-to-brain transport of circulating sA beta. Hence, sA beta can contribute to both cerebrovascular and parenchymal amyloid formation.
沉积在阿尔茨海默病（AD）患者大脑和脑血管中的β淀粉样蛋白（Aβ）的来源尚不清楚。在本研究中，我们测试了可溶性Aβ（sAβ）是否能够穿过血脑屏障（BBB）。我们采用豚鼠体内血管脑灌注模型和毛细血管耗竭技术，来确定与Aβ 1-40残基相同的合成肽（SP-40）在脑毛细血管中的滞留情况以及血脑转运情况。已证实在血脑屏障的管腔侧存在SP-40的可饱和、特异性结合，其解离常数（Kd）为25±2 nM，最大结合容量（Bmax）为188±11 fmol/（min·g）分离微血管。SP-40向脑实质的特异性跨细胞血脑屏障转运表现出米氏常数（Km）为49±10 nM，最大转运速率（Vmax）为111±19 fmol/（min·g）毛细血管耗竭脑。我们得出结论，血脑屏障有能力控制循环sAβ在脑血管中的滞留以及从血液到脑的转运。因此，sAβ可导致脑血管和脑实质淀粉样蛋白的形成。
