BRAIN and NERVE－神経研究の進歩62巻7号

2010年07月発行

増大特集 アルツハイマー病―研究と診療の進歩

病因分子としてのβアミロイド

著者： 富山貴美¹

所属機関： ¹大阪市立大学大学院医学研究科脳神経科学

ページ範囲：P.691 - P.699

文献概要

はじめに

　アルツハイマー病（Alzheimer disease：AD）の3大病理変化と言えば，老人斑，神経原線維変化，ニューロン消失である。この中では，老人斑が最も早く脳に出現する。老人斑は，AD，ダウン症，正常加齢の一部でのみみられ，疾患特異性も高い。これらのことから，ADの原因に最も近いのは，老人斑であろうと考えられた。その構成成分であるアミロイドβペプチド（Aβ）の凝集・沈着が，神経原線維変化やニューロン消失，ひいては認知機能低下を引き起こすのであろうと。この仮説は，「アミロイドカスケード仮説」（以下，アミロイド仮説）と名付けられ^1），多くの研究者によって支持されてきた。

　しかし，現在では，ADはAβの小さな集まりである可溶性のオリゴマーにその原因があると考えられている^2，3）。本稿では，この「オリゴマー仮説」がなぜ生まれてきたのか，また，アミロイド仮説からオリゴマー仮説への流れの中で，Aβ凝集体に対する考えがどのように変わってきたのかについて概説する。

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