Drexel University College of Medicine, Department of Neurobiology and Anatomy, Philadelphia, PA 19129, USA.
J Alzheimers Dis. 2012;28(2):241-81. doi: 10.3233/JAD-2011-110986.
Therapeutic options for Alzheimer's disease are currently limited to symptomatic treatment that only provides modest and temporary maintenance of cognitive and memory functions, without altering disease progression. Although a variety of therapeutics targeting amyloid production or plaque degradation as well as tau hyperphosphorylation and aggregation have been proposed, examined in pre-clinical models and introduced into clinical trials, many have failed to provide significant therapeutic benefit. Concerns over the adequacy of currently used pre-clinical models, in addition to questions pertaining to the timing of therapeutic administration, vis-à-vis synaptic and neuronal loss have been raised, and are further complicated by the genetic diversity of individual patients. This review will provide a brief overview of Alzheimer's disease pathophysiology and the currently approved therapeutics, while the main section will focus on therapeutics currently evaluated in pre-clinical models and clinical trials.
治疗阿尔茨海默病的方法目前仅限于对症治疗，只能适度且暂时维持认知和记忆功能，无法改变疾病进展。尽管已经提出了多种针对淀粉样蛋白生成或斑块降解以及过度磷酸化和聚集的 tau 治疗方法，并在临床前模型中进行了检验，也引入了临床试验，但许多方法都未能提供显著的治疗益处。目前使用的临床前模型是否充分，以及治疗的时机与突触和神经元丧失的关系，这些问题已经引起了人们的关注，而个体患者的遗传多样性又使问题变得更加复杂。这篇综述将简要概述阿尔茨海默病的病理生理学和目前批准的治疗方法，而主要部分将集中在目前在临床前模型和临床试验中评估的治疗方法。
