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) 在生物学上定义为存在含 β-淀粉样蛋白的斑块和含 tau 的神经原纤维缠结。AD 是一种遗传性和散发性神经退行性疾病，在其原型表现中会导致遗忘性认知障碍，在其不太常见的变体中会导致非遗忘性认知障碍。AD 是导致中年和晚年认知障碍的常见原因，但其临床影响会受到其他神经退行性疾病和脑血管疾病的影响。本 Primer 将 AD 生物学视为脑部疾病，由突触稳态丧失和高度相关的内体/溶酶体清除途径中的功能障碍的复杂相互作用引起，在该途径中，Aβ 和 tau 的前体、聚集物和翻译后修饰产物发挥作用重要的角色。