Department of Neurology, Mayo Clinic, Rochester, MN, USA.
Inserm U1219 Bordeaux Population Health Center, University of Bordeaux, Bordeaux, France.
Nat Rev Dis Primers. 2021 May 13;7(1):33. doi: 10.1038/s41572-021-00269-y.
Alzheimer disease (AD) is biologically defined by the presence of β-amyloid-containing plaques and tau-containing neurofibrillary tangles. AD is a genetic and sporadic neurodegenerative disease that causes an amnestic cognitive impairment in its prototypical presentation and non-amnestic cognitive impairment in its less common variants. AD is a common cause of cognitive impairment acquired in midlife and late-life but its clinical impact is modified by other neurodegenerative and cerebrovascular conditions. This Primer conceives of AD biology as the brain disorder that results from a complex interplay of loss of synaptic homeostasis and dysfunction in the highly interrelated endosomal/lysosomal clearance pathways in which the precursors, aggregated species and post-translationally modified products of Aβ and tau play important roles. Therapeutic endeavours are still struggling to find targets within this framework that substantially change the clinical course in persons with AD.
阿尔茨海默病（AD）在生物学上的定义是存在β-淀粉样蛋白含量斑块和含有 tau 的神经原纤维缠结。AD 是一种遗传和散发性神经退行性疾病，在其典型表现中引起健忘性认知障碍，在其不太常见的变体中引起非健忘性认知障碍。AD 是导致中年人及老年人获得性认知障碍的常见原因，但其他神经退行性和脑血管疾病会改变其临床影响。本指南将 AD 生物学视为一种大脑疾病，它是由于突触稳态丧失和高度相互关联的内体/溶酶体清除途径功能障碍之间复杂相互作用的结果，在该途径中，Aβ 和 tau 的前体、聚集物和翻译后修饰产物发挥重要作用。治疗工作仍在努力寻找该框架内的靶点，这些靶点可以实质性地改变 AD 患者的临床病程。
