Huffington Center on Aging, Department of Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
Curr Alzheimer Res. 2012 Feb;9(2):217-26. doi: 10.2174/156720512799361691.
Alzheimer's disease (AD) is the most common cause of dementia in aging populations. Although amyloid plaques are the hallmark of AD, loss of synapses and synaptic dysfunction are closely associated with the duration and severity of cognitive impairment in AD patients. Amyloid precursor protein (APP) and its cleavage products including Aβ have been suggested as homeostatic regulators of synaptic activity. APP manipulation and Aβ application, in vitro and in vivo, affect synapse formation and synaptic transmission. Moreover, synaptic dysfunction and learning deficits precede Aβ plaque deposition, suggesting that synaptic alterations may underlie the initial development of the disease. Because of the pivotal role of APP and Aβ in AD pathogenesis, it is essential to understand how APP and Aβ modulate synaptic function. Here, we review the roles that APP and Aβ play at the synapses, with particular focus on recent findings for the importance of APP in synaptogenesis and synaptic function.
阿尔茨海默病（AD）是老龄化人口中痴呆的最常见原因。虽然淀粉样斑块是 AD 的标志，但突触丧失和突触功能障碍与 AD 患者认知障碍的持续时间和严重程度密切相关。淀粉样前体蛋白（APP）及其切割产物包括 Aβ已被认为是突触活动的内稳态调节剂。APP 的操作和 Aβ的应用，无论是在体外还是体内，都会影响突触的形成和突触传递。此外，突触功能障碍和学习缺陷先于 Aβ斑块沉积，这表明突触改变可能是疾病最初发展的基础。由于 APP 和 Aβ在 AD 发病机制中的关键作用，了解 APP 和 Aβ如何调节突触功能至关重要。在这里，我们回顾了 APP 和 Aβ在突触中的作用，特别关注 APP 在突触发生和突触功能中的重要性的最新发现。
