Honig Lawrence S
Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Gertrude H. Sergievsky Center, New York, New York, USA.
Arch Neurol. 2012 Aug;69(8):969-77. doi: 10.1001/archneurol.2011.2883.
Dementia disorders are characterized by clinicopathological criteria. Molecular understandings of these disorders, based on immunohistochemical studies, biochemical investigations, genetic approaches, and animal models, have resulted in advances in diagnosis. Likewise, translational research has allowed us to apply our increasing basic scientific knowledge of neurodegeneration to the rational development of new investigational therapies based on our current understanding of disease pathogenesis. This review discusses the application of translational research to both diagnosis and treatment of dementia disorders. The development of biomarkers has yielded imaging and biochemical methods that assist the physician more than ever in the diagnosis of neurodegenerative dementias, especially Alzheimer disease. New diagnostic criteria for disease are based on these molecular-based techniques. And these biomarkers are of potential use in monitoring disease activity during therapeutic trials. Translational investigations likewise have led toward new avenues in targeted dementia research. This is particularly so in the development and testing of disease-modifying treatments that might slow or deter progressive deterioration. Recent clinical trials have not been based on empirical trials of established drugs but, rather, on trials of drugs shown, through experiments in biochemical, cell culture, and animal models, to interfere with known elements of the pathogenetic cascade of Alzheimer disease.
痴呆症是根据临床病理标准来界定的。基于免疫组化研究、生化研究、遗传学方法以及动物模型对这些疾病的分子层面的认识，已推动了诊断方面的进展。同样，转化研究使我们能够将日益增长的关于神经退行性变的基础科学知识，应用于基于当前对疾病发病机制的理解而合理开发新的研究性疗法。这篇综述讨论了转化研究在痴呆症诊断和治疗中的应用。生物标志物的发展产生了成像和生化方法，这些方法在诊断神经退行性痴呆，尤其是阿尔茨海默病方面，比以往任何时候都更有助于医生。基于这些分子技术制定了新的疾病诊断标准。而且这些生物标志物在治疗试验期间监测疾病活动方面具有潜在用途。转化研究同样为针对性痴呆研究开辟了新途径。在可能减缓或阻止病情进行性恶化的疾病修饰治疗的研发和测试中尤其如此。最近的临床试验并非基于现有药物的经验性试验，而是基于通过生化、细胞培养和动物模型实验显示能干扰阿尔茨海默病致病级联反应已知环节的药物试验。
