BRAIN and NERVE－神経研究の進歩65巻4号

2013年04月発行

増大特集 Antibody Update

アルツハイマー病に対するアミロイド免疫療法

著者： 坂井健二¹² 山田正仁¹

所属機関： ¹金沢大学大学院医薬保健学総合研究科脳老化・神経病態学（神経内科） ²

ページ範囲：P.461 - P.468

文献概要

はじめに

　アルツハイマー病は老人斑としての脳実質への不溶性アミロイドβ蛋白（amyloid β protein：Aβ）の沈着，神経原線維変化としての神経細胞内へのリン酸化タウ蛋白の蓄積，それらに伴う神経細胞死を特徴とする認知症性神経変性疾患である¹⁾。アミロイド前駆蛋白，presenilin-1やpresenilin-2といった遺伝子異常に伴う遺伝性の病型も報告されているが，ほとんどのアルツハイマー病は孤発性であり，加齢に伴い有病率が著しく増加することが特徴である。そのため，平均寿命が著しく伸びた先進諸国においては，介護といった社会的な問題のため，アルツハイマー病に対する有効な治療法の開発が急務となっている²⁾。

　現在，わが国で臨床的に使用可能なアルツハイマー病の治療薬は，病状の進行により脳内で低下するアセチルコリンを増加させたり，グルタミン酸レセプターを調節したりするといった，疾患の進行により機能低下を生じた神経細胞間の伝達を賦活化するものである。しかし，これらの治療法はアルツハイマー病の症状を一時的に緩和する効果しかなく，アルツハイマー病病変の進行を抑制することはできない。これらの治療法とは異なり，アルツハイマー病において中枢神経系に蓄積する異常蛋白を，免疫機能を利用することによって除去し，根本的な治療を行うことを企図したものがアルツハイマー病に対する免疫療法である。

　アルツハイマー病における免疫治療について，その臨床病理学的背景，動物実験や先行研究での結果，主な副作用，今後の展望について概説する。

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