Walker Lary C, Ibegbu Chris C, Todd Charles W, Robinson Harriet L, Jucker Mathias, LeVine Harry, Gandy Sam
Yerkes National Primate Research Center, Emory University, 954 Gatewood Road, Atlanta, GA 30322, USA.
Biochem Pharmacol. 2005 Apr 1;69(7):1001-8. doi: 10.1016/j.bcp.2004.12.015.
The currently approved therapies for Alzheimer's disease (AD) in the US are designed to modify the function of specific neurotransmitter systems in the brain. While these palliative treatments can benefit some patients for a period of time, they do not halt the relentless cognitive and behavioral deterioration that characterize this neurodegenerative disorder. Consequently, much current research on AD is directed toward illuminating the disease process itself, particularly the abnormal accumulation of certain proteins in brain: the amyloid-beta protein (Abeta) in senile plaques and cerebral blood vessels, and the tau protein in neurofibrillary tangles. Genetic, biochemical and pathologic evidence now favors a primary role of Abeta aggregation in the Alzheimer proteopathic cascade, and studies in mice indicate that lowering the amount of this protein in brain can be beneficial. Recently, Abeta-immunization therapy has emerged as a particularly promising therapeutic option for treating Alzheimer's disease, but unexpected treatment-related side-effects are an overriding issue. These adverse events were not anticipated from preclinical studies with rodents; hence, more biologically relevant models, such as nonhuman primates, are needed to test the safety and efficacy of novel therapies for Alzheimer's disease.
美国目前已获批的治疗阿尔茨海默病（AD）的疗法旨在改变大脑中特定神经递质系统的功能。虽然这些姑息性治疗在一段时间内可使部分患者受益，但它们无法阻止这种神经退行性疾病所特有的持续认知和行为衰退。因此，目前许多关于AD的研究都致力于阐明疾病过程本身，特别是某些蛋白质在大脑中的异常积聚：老年斑和脑血管中的β-淀粉样蛋白（Aβ），以及神经原纤维缠结中的tau蛋白。遗传、生化和病理学证据目前支持Aβ聚集在阿尔茨海默病蛋白病级联反应中起主要作用，并且对小鼠的研究表明，降低大脑中这种蛋白质的含量可能有益。最近，Aβ免疫疗法已成为治疗阿尔茨海默病特别有前景的治疗选择，但与治疗相关的意外副作用是一个首要问题。这些不良事件在对啮齿动物的临床前研究中并未预料到；因此，需要更具生物学相关性的模型，如非人灵长类动物，来测试治疗阿尔茨海默病新疗法的安全性和有效性。
