Hardy J, Allsop D
Department of Biochemistry and Molecular Genetics, St Mary's Hospital Medical School, London, UK.
Trends Pharmacol Sci. 1991 Oct;12(10):383-8. doi: 10.1016/0165-6147(91)90609-v.
While there may be many causes of Alzheimer's disease (AD), the same pathological sequence of events, described here by John Hardy and David Allsop, is likely to occur in all cases. The recent discovery of a pathogenic mutation in the beta-amyloid precursor protein (APP) gene on chromosome 21 suggests that APP Mismetabolism and beta-amyloid deposition are the primary events in the disease process. The occurrence of AD in Down syndrome is consistent with this hypothesis. The pathological cascade for the disease process is most likely to be: beta-amyloid deposition----tau phosphorylation and tangle formation----neuronal death. The development of a biochemical understanding of this pathological cascade will facilitate rational design of drugs to intervene in this process.
虽然阿尔茨海默病（AD）可能有多种病因，但约翰·哈迪和大卫·奥尔索普在此描述的相同病理事件序列可能在所有病例中都会发生。最近在21号染色体上的β-淀粉样前体蛋白（APP）基因中发现了致病突变，这表明APP代谢异常和β-淀粉样蛋白沉积是疾病过程中的主要事件。唐氏综合征中AD的发生与这一假说相符。该疾病过程的病理级联反应很可能是：β-淀粉样蛋白沉积——tau蛋白磷酸化和缠结形成——神经元死亡。对这一病理级联反应进行生化层面的理解将有助于合理设计干预这一过程的药物。
