DOROTHY-RUSSELL-MEMORIAL-LECTURE - THE MOLECULAR PATHOLOGY OF ALZHEIMERS-DISEASE - ARE WE ANY CLOSER TO UNDERSTANDING THE NEURODEGENERATIVE PROCESS
DOROTHY-RUSSELL-MEMORIAL-LECTURE - THE MOLECULAR PATHOLOGY OF ALZHEIMERS-DISEASE - ARE WE ANY CLOSER TO UNDERSTANDING THE NEURODEGENERATIVE PROCESS
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DOI：
10.1111/j.1365-2990.1994.tb00977.x
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发表时间：
1994-08-01
影响因子：
5
通讯作者：
ANDERTON, BH
中科院分区：
文献类型：
--
作者：
SMITH, C;ANDERTON, BH
阿尔茨海默病是导致老年人痴呆症的最常见原因，在西方世界迅速流行，对社会和经济产生了重大影响。因此，国际上正在作出巨大的科学努力，以增加我们对这种疾病的发病机制的了解，最终目标是开发有益的治疗方法。阿尔茨海默病(AD)的两个主要神经病理特征是细胞外老年斑和神经元内神经纤维缠结，前者的主要成分是AP淀粉样肽，后者是以成对螺旋细丝(PHF)的形式聚集的tau蛋白。在过去的十年里，随着这些病理标志物的主要蛋白质成分的确定，在阐明其在阿尔茨海默病中异常沉积和聚集的生化过程方面取得了很大进展。与此同时，广泛的群体遗传学分析已经在少数家族性阿尔茨海默病(FAD)家系中发现了Aβ淀粉样前体蛋白(APP)的突变，而其他FAD病例已被发现与14号染色体上的一个未知标记有关。最近，载脂蛋白E的4型等位基因的遗传也被确定为散发性AD的危险因素。科学家现在面临的挑战是将这些令人兴奋的新生化和遗传数据整合到一个连贯的模型中，该模型可以解释阿尔茨海默病长期存在的神经化学和组织病理学损害。
Alzheimer's disease, the most common cause of dementia in the elderly, is rapidly becoming epidemic in the western world, with major social and economic ramifications. Thus enormous international scientific efforts are being made to increase our understanding of the pathogenesis of this disease, with the eventual goal of developing beneficial therapy. The two major neuropathological hallmarks of Alzheimer's disease (AD) are extracellular senile plaques, the principal component of which is the AP amyloid peptide, and intraneuronal neurofibrillary tangles, which are composed of aggregated tau protein in the form of paired helical filaments (PHF). In the past decade, since the major proteinaceous components of these pathological markers have been identified, great strides have been made in elucidating the biochemical processes which may underlie their abnormal deposition and aggregation in Alzheimer's disease. Simultaneously, extensive population genetic analyses have identified mutations in the A beta amyloid precursor protein (APP) in a small number of pedigrees with familial Alzheimer's disease (FAD) whilst other FAD cases have been linked to an, as yet, unidentified marker on chromosome 14. Most recently, inheritance of the type 4 allele of apolipoprotein E has also been identified as a risk factor in sporadic AD. The challenge facing scientists now is to incorporate this wealth of exciting new biochemical and genetic data into a coherent model which can explain the long established neurochemical and histopathological lesions characteristic of AD.