アルツハイマー病のワクチン療法

Vaccination Therapy for Alzheimer's Disease

はじめに

　アルツハイマー病（Alzheimer's disease：AD）は大脳の変性疾患であり，記憶障害で始まり認知症が徐々に進行する。高齢者に好発し，加齢とともに幾何級数的に増加するので加齢が最大の危険因子となっている。しかし，90歳以降はその頻度はむしろ減少するので，脳の究極の加齢ではない。脳には老人斑と呼ばれる特徴ある変化がみられ，そこにはベータ（β）アミロイドが沈着している。このβアミロイドはADの病態形成において中核的存在であると考えられ，アミロイド仮説が提唱されている。近年，このβアミロイドで免疫すると老人斑が消失し，新たな形成も阻止されることがわかり，ワクチン療法として注目されている。ここではアルツハイマー病のワクチン療法の開発状況を紹介する。

Abstract

　Alzheimer's disease is a neurodegenerative disorder characterized by senile plaques in the brain.　In the senile plaques beta-amyloid is deposited and neuroinflammation due to innate immune responses against beta-amyloid is thought to cause degeneration of synapses and neural processes.　In 1999 Dale Schenk et al. discovered that immunization of amyloid precursor protein (APP) transgenic mice with amyloid-beta protein (A-beta) reduces senile plaques and prevents new deposits of beta-amyloid.　They also have found that antibodies to A-beta have similar effect.　Since immunized mice showed improvement of cognitive functions, an active immunization method was tested in humans.　However, the trial was halted because of side effect, subacute meningoencephalitis due to T-cell mediated autoimmune responses.　We developed a safe oral A-beta vaccine using adeno-associated virus vector.　When this vaccine was given once, antibodies were elevated well and high titers were kept for over 6 months.　APP transgenic mice and old monkeys showed significant reduction of amyloid burden without any side effect.　Since Th1 immune responses are suppressed in the gut immune system, this is a promising way to treat and prevent Alzheimer's disease.