Peskind E R
Department of Psychiatry and Behavioral Sciences, University of Washington, School of Medicine, Seattle, USA.
J Clin Psychiatry. 1996;57 Suppl 14:5-8.
Although the specific process that destroys neurons in patients with Alzheimer's disease (AD) remains obscure, biochemical studies of AD neurohistologic lesions and molecular attempts to map and clone genes in familial AD have contributed greatly to our knowledge of AD. The major component of the extraneuronal neuritic plaque is beta-amyloid (A beta), which may be neurotoxic. The major component of the intraneuronal neurofibrillary tangle is hyperphosphorylated tau protein. It is unclear why this process damages the neuronal cytoskeleton Familial AD is genetically heterogeneous. Chromosomes 21, 14, and 1 are causative genes in early-onset familial AD. The apolipoprotein E4 allele of chromosome 19 is a risk factor for both early- and late-onset AD. Unraveling the actions of these three causative genes and the apolipoprotein E4 allele may explain disease mechanisms common to all patients with AD.
尽管阿尔茨海默病（AD）患者神经元被破坏的具体过程仍不清楚，但对AD神经组织学病变的生化研究以及对家族性AD基因进行定位和克隆的分子学尝试，极大地增进了我们对AD的了解。细胞外神经炎性斑块的主要成分是β-淀粉样蛋白（Aβ），它可能具有神经毒性。细胞内神经原纤维缠结的主要成分是过度磷酸化的tau蛋白。目前尚不清楚为何这一过程会损害神经元细胞骨架。家族性AD在遗传上具有异质性。21号、14号和1号染色体上的基因是早发性家族性AD的致病基因。19号染色体上的载脂蛋白E4等位基因是早发性和晚发性AD的一个风险因素。弄清楚这三个致病基因和载脂蛋白E4等位基因的作用，可能会解释所有AD患者共有的疾病机制。
