Immune targeting of apolipoprotein E in amyloid deposits ; a fundamental study using murine model

淀粉样变性通常在活检标本上进行组织学诊断。然而，这种方法不仅是侵入性的，而且无法评估全身淀粉样蛋白沉积的量和定位。已知载脂蛋白（apoE）存在于沉积物中。为了开发新的诊断工具，本研究以apoE为靶点。利用表达人apoE的小鼠和识别人apoE片段的单克隆抗体，标记抗体在体内与沉积物有效结合，并通过免疫化学方法证实其在沉积物中的定位。然而，在成像研究后，给予的放射性背景较高。抗体的血浆半衰期在淀粉样变性小鼠中没有缩短。给予抗体并不能阻止小鼠淀粉样变性的发展，也不能促进已经存在的淀粉样沉积物的吸收，这些结果表明该策略本身是合理的，但抗体可以改进以具有与淀粉样沉积物更强的亲和力。

Amyloidosis is usually diagnosed histologically on biopsy specimens. However, this approach is not only invasive but also is unable to evaluate the amount and localization of amyloid deposits in the whole body. Apolipoprotein (apoE) is known to be present in the deposits. Aiming to develop the new diagnostic tool, in this study, apoE was focused as a target. Human apoE expressing mouse and a monoclonal antibody recognizing human apoE fragment were utilized.Labeled antibody efficiently bound to the deposits in vivo and its localization in the deposits was confirmed immunohistochemically. However, high background of administered radioactivity could not follow the imaging study. The plasma half life of the antibody was not shortened in the amyloidotic mouse. Administration of antibody did not prevent the mouse from amyloidosis development or enhance the absorption of already present amyloid deposits.These results indicate that the strategy itself is reasonable but the antibody may be improved to have the stronger affinity with the amyloid deposits.