Shayo M, McLay R N, Kastin A J, Banks W A
VA Medical Center, New Orleans LA 70146, USA.
Life Sci. 1997;60(7):PL115-8. doi: 10.1016/s0024-3205(96)00685-6.
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, 125I-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.
β-淀粉样蛋白（Aβ）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，存在于血液中且能够穿过血脑屏障（BBB）。这表明循环系统可能是大脑中Aβ的一个来源。未结合的Aβ穿过血脑屏障的速度很慢。然而，血液中的大多数Aβ可能与载脂蛋白J（ApoJ）结合。在用无血脑灌注模型进行原位研究时，已表明与ApoJ结合的ApoJ和Aβ能够快速穿过豚鼠的血脑屏障。然而，血液中ApoJ的浓度比原位饱和ApoJ转运体所需浓度高28倍。这表明假定的ApoJ转运体在体内可能不起作用。我们在此发现，在小鼠原位脑灌注模型中测量时，125I-ApoJ以3.75×10⁻³ ml/g·min的单向流入速率常数（Ki）穿过血脑屏障，这与在豚鼠中发现的相似。然而，静脉注射后，在小鼠或豚鼠中均未检测到ApoJ穿过血脑屏障。这些结果表明，ApoJ不太可能在体内为Aβ穿过血脑屏障提供一条重要途径。
