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

淀粉样变通常在活检标本上进行组织学诊断。然而，这种方法不仅具有侵入性，而且无法评估淀粉样蛋白沉积在全身的数量和定位。已知载脂蛋白（apoE）存在于沉积物中。为了开发新的诊断工具，本研究重点以apoE为靶点。利用人apoE表达小鼠和识别人apoE片段的单克隆抗体。标记抗体在体内与沉积物有效结合，免疫组织化学证实其在沉积物中的定位。然而，高本底放射性不能跟随成像研究。在淀粉样变小鼠中，抗体的血浆半衰期没有缩短。注射抗体并不能阻止小鼠淀粉样变性的发展，也不能增强对已经存在的淀粉样沉积的吸收。这些结果表明，该策略本身是合理的，但可以改进抗体，使其与淀粉样蛋白沉积物具有更强的亲和力。

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.