Itzhaki Ruth F, Cosby S Louise, Wozniak Matthew A
Faculty of Life Sciences, The University of Manchester, Manchester, UK.
J Neurovirol. 2008 Jan;14(1):1-4. doi: 10.1080/13550280701802543.
The causes of Alzheimer's disease (AD) and of the characteristic pathological features - amyloid plaques and neurofibrillary tangles - of AD brain are unknown, despite the enormous resources provided over the years for their investigation. Indeed, the only generally accepted risk factors are age, Down syndrome, carriage of the type 4 allele of the apolipoprotein E gene (APOE-epsilon 4), and possibly brain injury. Following the authors' previous studies implicating herpes simplex virus type 1 (HSV1) in brain of APOE-epsilon 4 carriers as a major cause of AD, the authors propose here, on the basis of their and others' recent studies, that not only does HSV1 generate the main components of amyloid plaques and neurofibrillary tangles (NFTs) - beta-amyloid (A beta) and abnormally phosphorylated tau but also, by disrupting autophagy, it prevents degradation of these aberrant proteins, leading to their accumulation and deposition, and eventually to AD.
尽管多年来投入了大量资源进行研究，但阿尔茨海默病（AD）的病因以及AD大脑的特征性病理特征——淀粉样斑块和神经原纤维缠结——仍不清楚。事实上，唯一被普遍认可的风险因素是年龄、唐氏综合征、载脂蛋白E基因（APOE-ε4）4型等位基因的携带，以及可能的脑损伤。在作者之前的研究表明1型单纯疱疹病毒（HSV1）在APOE-ε4携带者的大脑中是AD的主要病因之后，基于他们自己和其他人最近的研究，作者在此提出，HSV1不仅产生淀粉样斑块和神经原纤维缠结（NFTs）的主要成分——β-淀粉样蛋白（Aβ）和异常磷酸化的tau蛋白，而且通过破坏自噬，阻止这些异常蛋白质的降解，导致它们的积累和沉积，最终引发AD。
