The putative blood-brain barrier transporter for the beta-amyloid binding protein apolipoprotein J is saturated at physiological concentrations
The putative blood-brain barrier transporter for the beta-amyloid binding protein apolipoprotein J is saturated at physiological concentrations
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DOI：
10.1016/s0024-3205(96)00685-6
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发表时间：
1997-01-10
期刊：
影响因子：
6.1
通讯作者：
Banks, WA
中科院分区：
文献类型：
--
作者：
Shayo, M;McLay, RN;Banks, WA
β-淀粉样蛋白（A β）是阿尔茨海默病患者大脑中沉积的淀粉样蛋白的主要成分，存在于血液中，可以穿过血脑屏障（BBB）。这表明循环可能是大脑中A β的来源。未结合的A β穿过BBB是缓慢的。然而，血液中的大多数A β可能与载脂蛋白J（ApoJ）结合。当用无血脑灌注模型原位研究时，ApoJ和与ApoJ结合的A β已显示出快速穿过豚鼠的BBB。然而，血液中的ApoJ浓度比原位饱和ApoJ转运蛋白所需的浓度高28倍。这表明推定的ApoJ转运蛋白在体内可能没有功能。我们发现，当在小鼠原位脑灌注模型中测量时，I-125-ApOJ以3.75 x 10（-3）ml/g-min的单向流入速率常数（Ki）穿过BBB，这与在豚鼠中发现的结果相似。然而，静脉注射后，在小鼠或豚鼠中均未测量到ApoJ穿过BBB的渗透。这些结果表明，ApoJ不太可能为A β在体内穿过BBB的转运提供重要途径。
beta-amyloid (A beta), the major component of the amyloid deposited in the brains of patients with Alzheimer's disease, is found in blood and can cross the blood-brain barrier (BBB). This suggests that the circulation could be a source of A beta in brain. The passage of unbound A beta across the BBB is slow. Most of the A beta in blood, however, is likely to be bound to apolipoprotein J (ApoJ). ApoJ and A beta bound to ApoJ have been shown to rapidly cross the BBB of the guinea pig when studied in situ with a blood-free brain perfusion model. ApoJ in blood, however, is found in a concentration 28 times higher than that needed to saturate the ApoJ transporter in situ. This suggests that the putative ApoJ transporter may not be functional in vivo. We found here that when measured in a murine in situ brain perfusion model, I-125-ApOJ crossed the BBB with a unidirectional influx rate constant (Ki) of 3.75 x 10(-3) ml/g-min, which is similar to that found in the guinea pig. After intravenous injection, however, no penetration of ApoJ across the BBB was measured in either the mouse or guinea pig. These results suggest that ApoJ is unlikely to provide a significant route for the transport of A beta across the BBB in vivo.