Rojas-Fernandez Carlos H, Chen Ming, Fernandez Hugo L
Department of Pharmacy Practice, School of Pharmacy, Texas Tech University Health Sciences Center, 1300 Coulter, Amarillo, TX 79106-1712, USA.
Pharmacotherapy. 2002 Dec;22(12):1547-63. doi: 10.1592/phco.22.17.1547.34116.
Alzheimer's disease is the most common type of dementia in older people. It is highly prevalent, affecting 35-45% of those aged 85 years or older. This disease has devastating consequences to patients, their families, caregivers, and the health care system. Much has been learned about its pathobiology, which has led to the beta-amyloid (Abeta) hypothesis. This hypothesis continues to be the predominant postulate of the pathobiology of Alzheimer's disease. Under this hypothesis, abnormal accumulation of Abeta is followed by a cascade of neurotoxic effects, which eventually result in neurodegeneration and development of Alzheimer's disease. This is thought to be the result of altered processing of the amyloid precursor protein (APP), preferentially by beta- and gamma-secretase enzymes rather than nonamyloidogenic processing by alpha-secretase. The growing body of knowledge regarding the processing of APP to various forms of Abeta has resulted in new approaches to the investigation of putative anti-Alzheimer's disease compounds, including immune-based therapies and various agents that can positively affect APP processing.
阿尔茨海默病是老年人中最常见的痴呆类型。它极为普遍，影响着35%至45%的85岁及以上老人。这种疾病给患者、其家人、护理人员以及医疗保健系统带来了毁灭性后果。人们对其病理生物学已有很多了解，这催生了β-淀粉样蛋白（Aβ）假说。该假说仍然是阿尔茨海默病病理生物学的主要假设。在这个假说下，Aβ的异常积聚之后会引发一系列神经毒性作用，最终导致神经退行性变和阿尔茨海默病的发展。这被认为是淀粉样前体蛋白（APP）加工过程改变的结果，优先由β-和γ-分泌酶进行加工，而不是由α-分泌酶进行非淀粉样生成加工。关于APP加工成各种形式Aβ的知识不断增加，催生了研究潜在抗阿尔茨海默病化合物的新方法，包括基于免疫的疗法以及各种能对APP加工产生积极影响的药物。
