Department of Public Health and Primary Care, Institute of Public Health, University of Cambridge, Forvie Site, Robinson Way, Cambridge, United Kingdom.
CNS Neurosci Ther. 2010 Aug;16(4):254-62. doi: 10.1111/j.1755-5949.2009.00117.x. Epub 2009 Apr 16.
The amyloid cascade hypothesis, based on the genetic data from early onset, familial forms of the disease, has been the dominant model for many years and involves over production and deposition of the beta amyloid protein as causal in the disease process. However, it does not apply very well to the more common, later onset, sporadic form of the disease, where a wider range of factors appear to be involved in disease progression. Over recent years, data illustrating reciprocal interactions between the amyloid precursor protein (APP) and its various metabolites with many factors involved in normal synaptic plasticity have emerged. These feedback relationships have the potential to affect the complex kinase cascades involved in every aspect of neuronal function. Further, data regarding the multiple roles of the presenilins have the potential to allow the over expression and deposition of the amyloid beta protein to be both a cause and consequence of disease progression, with relevance in both sporadic and familial of Alzheimer's disease (AD). Disease progression might be better explained by a chaotic matrix of factors and raises the question again whether AD should be approached as a single entity or as a syndrome, with important consequences for disease identification and treatment.
淀粉样蛋白级联假说，基于早发性、家族性疾病的遗传数据，多年来一直是占主导地位的模型，涉及β淀粉样蛋白的过度产生和沉积，这在疾病过程中是致病的。然而，它并不能很好地应用于更为常见的、发病较晚的散发性疾病，在这种疾病中，涉及到更多的因素。近年来，有数据表明淀粉样前体蛋白 (APP) 及其各种代谢物与正常突触可塑性涉及的许多因素之间存在相互作用。这些反馈关系有可能影响到涉及神经元功能各个方面的复杂激酶级联反应。此外，关于早老素的多种作用的数据有可能使β淀粉样蛋白的过度表达和沉积既成为疾病进展的原因，也成为其结果，这与散发性和家族性阿尔茨海默病 (AD) 都有关。疾病进展可能更好地用一个混沌的因素矩阵来解释，并再次提出 AD 是否应该被视为一个单一的实体或综合征来进行研究的问题，这对疾病的识别和治疗具有重要意义。
