Govaerts L, Schoenen J, Bouhy D
Universite de Liège, Belgique.
Rev Med Liege. 2007 Apr;62(4):209-16.
Alzheimer's disease is worldwide the leading cause of dementia in the elderly. Senile plaques and neurofibrillary tangles are together with neuronal loss and cortical atrophy characteristic neuropathological features of the disease. Senile plaques contain beta-amyloid (Abeta) peptide which is produced by cleavage of the amyloid precursor protein (APP) by beta- and gamma-secretases. Neurofibrillary tangles are twisted helicoidal strands of hyperphosphorylated tau protein, a microtubule-associated protein. Both pathogenic arms which we describe are interrelated and Abeta deposition seems to potentiate tau pathology. Tangle and plaque formation is influenced by various factors including reciprocal interactions, genetic factors, inflammation and reactive oxygen species. A better understanding of the cellular and molecular cascade which leads to the neuropathological lesions of Alzheimer's disease has led to novel disease-modifying treatment strategies. They yield varying, though encouraging, results and target various stages of the pathological process. Future cooperation between basic, clinical and pharmacological research should allow the development in a foreseeable future of strategies that can halt, or even prevent, this devastating disorder.
阿尔茨海默病是全球老年人痴呆的主要病因。老年斑和神经原纤维缠结以及神经元丢失和皮质萎缩是该疾病典型的神经病理学特征。老年斑含有β-淀粉样蛋白（Aβ）肽，它是由淀粉样前体蛋白（APP）经β-和γ-分泌酶切割产生的。神经原纤维缠结是高度磷酸化的tau蛋白（一种微管相关蛋白）扭曲的螺旋状丝。我们所描述的这两种致病途径相互关联，Aβ沉积似乎会增强tau病理改变。缠结和斑块的形成受多种因素影响，包括相互作用、遗传因素、炎症和活性氧。对导致阿尔茨海默病神经病理损伤的细胞和分子级联反应有了更好的理解，从而产生了新的疾病修饰治疗策略。这些策略产生了不同但令人鼓舞的结果，并针对病理过程的各个阶段。基础研究、临床研究和药理学研究未来的合作应能在可预见的未来开发出能够阻止甚至预防这种毁灭性疾病的策略。
