Turner R Scott
Neurology Service, VA Ann Arbor Healthcare System, Michigan 48105, USA.
Semin Neurol. 2006 Nov;26(5):499-506. doi: 10.1055/s-2006-951622.
Alzheimer's disease (AD) is the most commonly diagnosed etiology of dementia and may be caused by the progressive accumulation and deposition of neurotoxic Abeta/amyloid plaques and aggregates in brain with aging-the amyloid hypothesis of AD. However, Abeta/amyloid deposition is likely necessary but not sufficient to cause AD, and other putative downstream pathologies, including the aggregation of phospho-tau in neurofibrillary tangles, synaptic and neuronal loss, and glial and inflammatory responses, are likely equally important to AD pathogenesis. The majority of AD is sporadic (> 95%) but the discovery of rare early onset familial forms of AD has been pivotal to our understanding of its pathogenesis and in developing novel therapeutic strategies. Currently available drugs for patients with AD provide modest, temporary, and palliative benefits, but they consistently demonstrate safety and efficacy on cognitive, functional, behavioral, and global outcome measures. Novel potential disease-modifying therapies now in preclinical research or clinical trials may be more effective in preventing or arresting the progressive dementia of AD and will provide a test of the amyloid hypothesis.
阿尔茨海默病（AD）是最常被诊断出的痴呆病因，可能是由于随着年龄增长，神经毒性β-淀粉样蛋白/淀粉样斑块在大脑中逐渐积累和沉积所致——这就是AD的淀粉样蛋白假说。然而，β-淀粉样蛋白/淀粉样沉积可能是引发AD的必要但非充分条件，其他假定的下游病理变化，包括神经原纤维缠结中磷酸化tau蛋白的聚集、突触和神经元丧失以及神经胶质和炎症反应，对AD发病机制可能同样重要。大多数AD是散发性的（>95%），但罕见的早发性家族性AD的发现对于我们理解其发病机制以及开发新的治疗策略至关重要。目前用于AD患者的药物只能提供适度、暂时和姑息性的益处，但它们在认知、功能、行为和整体预后指标方面始终显示出安全性和有效性。目前处于临床前研究或临床试验阶段的新型潜在疾病修饰疗法可能在预防或阻止AD的进行性痴呆方面更有效，并将对淀粉样蛋白假说进行验证。
