Riekkinen P, Schmidt B H, van der Staay F J
University of Kuopio and Kuopio University Hospital, Department of Neuroscience and Neurology, Finland.
Ann Med. 1998 Dec;30(6):566-76. doi: 10.3109/07853899809002606.
Dementia of the Alzheimer type (AD) is clinically characterized by a progressive deterioration of intellect, memory, judgment, and abstract thinking. It is incurable, and causal therapy is not yet available. For the development of therapeutic drugs, valid animal models are needed that mimic the pathophysiological change in brain functions and the concomitant behavioural deterioration seen in AD patients. This article provides an overview of the animal models that are used most often to study the substrates and mechanisms of the pathological changes underlying AD and to identify, characterize and develop putative neuroprotective, antidegenerative, revalidation-supporting and/or cognition-enhancing compounds or treatments. The first generation of agents for the symptomatic treatment of the disease has been developed on the basis of results obtained with these models. These drugs are presently undergoing clinical testing or are already used therapeutically. There is, however, no single animal model that can mimic the full range of pathophysiological alterations and key symptoms of AD. New, genetically engineered mouse models that mimic at least some of the key pathological changes of AD are expected to provide tools that will facilitate the development of symptomatic and preventive drug therapies.
阿尔茨海默病型痴呆（AD）的临床特征是智力、记忆、判断力和抽象思维的进行性衰退。它无法治愈，且尚无因果疗法。为了开发治疗药物，需要有效的动物模型来模拟AD患者大脑功能的病理生理变化以及伴随的行为衰退。本文概述了最常用于研究AD潜在病理变化的底物和机制，以及鉴定、表征和开发假定的神经保护、抗退变、再验证支持和/或认知增强化合物或治疗方法的动物模型。基于这些模型所获得的结果，已开发出第一代用于该疾病症状治疗的药物。这些药物目前正在进行临床试验或已用于治疗。然而，没有单一的动物模型能够模拟AD的全部病理生理改变和关键症状。有望出现至少能模拟AD一些关键病理变化的新型基因工程小鼠模型，为开发对症和预防性药物疗法提供便利工具。
