Pan Weihong, Solomon Beka, Maness Lawrence M, Kastin Abba J
Veterans Affairs Medical Center and Department of Medicine, Tulane University School of Medicine, New Orleans, Louisiana 70112, USA.
Exp Biol Med (Maywood). 2002 Sep;227(8):609-15. doi: 10.1177/153537020222700808.
Amyloid-beta peptides (Abeta) play an important role in the pathophysiology of dementia of the Alzheimer's type and in amyloid angiopathy. Abeta outside the CNS could contribute to plaque formation in the brain where its entry would involve interactions with the blood-brain barrier (BBB). Effective antibodies to Abeta have been developed in an effort to vaccinate against Alzheimer's disease. These antibodies could interact with Abeta in the peripheral blood, block the passage of Abeta across the BBB, or prevent Abeta deposition within the CNS. To determine whether the blocking antibodies act at the BBB level, we examined the influx of radiolabeled Abeta (125I-Abeta(1-40)) into the brain after ex-vivo incubation with the antibodies. Antibody mAb3D6 (élan Company) reduced the blood-to-brain influx of Abeta after iv bolus injection. It also significantly decreased the accumulation of Abeta in brain parenchyma. To confirm the in-vivo study and examine the specificity of mAb3D6, in-situ brain perfusion in serum-free buffer was performed after incubation of 125I-Abeta(1-40) with another antibody mAbmc1 (DAKO Company). The presence of mAbmc1 also caused significant reduction of the influx of Abeta into the brain after perfusion. Therefore, effective antibodies to Abeta can reduce the influx of Abeta(1-40) into the brain.
β-淀粉样肽（Aβ）在阿尔茨海默病型痴呆的病理生理学以及淀粉样血管病中发挥着重要作用。中枢神经系统（CNS）外的Aβ可能会导致大脑中斑块的形成，其进入大脑的过程涉及与血脑屏障（BBB）的相互作用。为了研发针对阿尔茨海默病的疫苗，人们已经开发出了有效的抗Aβ抗体。这些抗体可以与外周血中的Aβ相互作用，阻止Aβ穿过血脑屏障，或者防止Aβ在中枢神经系统内沉积。为了确定阻断抗体是否在血脑屏障水平起作用，我们在抗体进行体外孵育后，检测了放射性标记的Aβ（125I-Aβ(1-40)）进入大脑的情况。抗体mAb3D6（伊兰公司）在静脉推注后减少了Aβ从血液到大脑的流入。它还显著降低了Aβ在脑实质中的积累。为了证实体内研究并检验mAb3D6的特异性，在将125I-Aβ(1-40)与另一种抗体mAbmc1（达科公司）孵育后，在无血清缓冲液中进行了原位脑灌注。mAbmc1的存在在灌注后也导致Aβ流入大脑的量显著减少。因此，有效的抗Aβ抗体可以减少Aβ(1-40)流入大脑。
