Zlokovic B V, Martel C L, Mackic J B, Matsubara E, Wisniewski T, McComb J G, Frangione B, Ghiso J
Department of Neurological Surgery, Childrens Hospital Los Angeles, USC School of Medicine 90033.
Biochem Biophys Res Commun. 1994 Dec 15;205(2):1431-7. doi: 10.1006/bbrc.1994.2825.
Amyloid beta (A beta) is a fibrillar component in Alzheimers' disease amyloid deposits and a soluble peptide (sA beta) normally present in body fluids. We have recently reported that the blood-brain barrier (BBB) has a capability to control cerebrovascular sequestration and transport of circulating sA beta. In this study, we examined whether two circulating amyloid-associated proteins shown to bind sA beta, apolipoproteins J (apo J) and E (apo E), can cross the BBB alone and/or complexed to a synthetic peptide homologous to a major form of sA beta, sA beta 1-40. Brain perfusion experiments in guinea pigs showed significant uptake of both apo J and sA beta 1-40-apo J complexes. In contrast, blood-brain transport of sA beta 1-40-apo E was negligible, while apo E had a limited access across the BBB, indicating that the apo E found within the brain is produced locally. It is concluded that sA beta 1-40 binding to apo J and apo E results in significant (> 100-fold) difference in brain uptake of their respective complexes. We hypothesize that in normal brain apo J facilitates sA beta transport.
淀粉样β蛋白（Aβ）是阿尔茨海默病淀粉样沉积物中的一种纤维成分，也是一种通常存在于体液中的可溶性肽（sAβ）。我们最近报道，血脑屏障（BBB）具有控制脑血管对循环中sAβ的隔离和转运的能力。在本研究中，我们检测了两种已证明能结合sAβ的循环淀粉样相关蛋白，载脂蛋白J（apo J）和E（apo E），是否能单独穿过血脑屏障，以及/或者与一种与主要形式的sAβ，即sAβ1-40同源的合成肽形成复合物后穿过血脑屏障。豚鼠的脑灌注实验显示apo J和sAβ1-40-apo J复合物均有显著摄取。相比之下，sAβ1-40-apo E的血脑转运可忽略不计，而apo E穿过血脑屏障的能力有限，这表明脑内发现的apo E是在局部产生的。结论是，sAβ1-40与apo J和apo E的结合导致它们各自复合物在脑摄取上存在显著（>100倍）差异。我们推测，在正常脑内，apo J促进sAβ的转运。
