Abstract:

Alzheimer's disease (AD) becomes a major disease affecting the elderly with high prevalence. However, no disease-modifying therapies are currently available. AD has long been regarded as a disease of brain itself, but recent studies found that systemic disorders are associated with risk for AD. During the period of Twelfth Five-Year Plan for National Economic and Social Development, our team tried to reveal the pathogenesis, targets, amyloid β-protein (Aβ) clearence pathway and drugs from both central and peripheral approaches, and have discovered: 1) the ratio of p75 neurotrophin receptor (p75NTR) in the brain of AD regulates the over?production and clearence of Aβ in sporadic AD. 2) Peripheral Aβ is able to enter brain, forms AD-type pathologies and induces neuronal deficits, revealing the peripheral mechanism of AD. 3) The effectiveness and safety of brain A β clearance by peripheral organs and tissues has been verified. Based on these findings, we proposed a systemic view of AD, to understand pathogenesis and develop novel diagnostic methods and therapies from a systemic approach.

Key words: Alzheimer disease, Amyloid beta-protein, China, Review

摘要：

阿尔茨海默病患病率高，是影响老年人群健康的重要疾病，目前尚无有效预防与治疗方法。传统认为，阿尔茨海默病是中枢神经系统疾病；近年研究显示，系统因素与阿尔茨海默病存在密切关系。我国国民经济和社会发展第十二个五年规划（简称“十二五”）时期，第三军医大学大坪医院王延江教授研究团体从中枢和外周两种途径探讨阿尔茨海默病发病机制、干预靶点、β?淀粉样蛋白（Aβ）清除途径和药物：（1）揭示神经营养因子受体p75 调控脑组织Aβ过度产生和清除的新机制。（2）发现外源性Aβ进入脑组织参与阿尔茨海默病的发生与发展，揭示阿尔茨海默病的外周机制。（3）证实外周途径清除Aβ的有效性，提出外周途径清除Aβ的阿尔茨海默病预防与治疗新策略。进而在上述研究基础上提出阿尔茨海默病系统观，为从全身角度探讨疾病发病机制及诊断与治疗策略提供新的思路。

关键词: 阿尔茨海默病, 淀粉样β蛋白, 中国, 综述