Wisniewski T, Frangione B
Department of Neurology, New York University Medical Center, NY 10016, USA.
Acta Neurobiol Exp (Wars). 1996;56(1):267-79. doi: 10.55782/ane-1996-1132.
A significant component of the aging process is genetically determined. Numerous theories of aging exist, many of which postulate the existence of "longevity genes." Recent advances in molecular biological and other techniques have allowed a significantly greater understanding of aging and age-related disease. This will be illustrated by four genetic and sporadic diseases: Alzheimer's disease (AD) and related disorders, transthyretin dementia, cerebral amyloid angiopathy-Icelandic type and scrapie related diseases. Alzheimer's disease (AD), the most common of this group, is the leading cause of dementia in Western countries. Recent genetic and biochemical studies have shown the involvement of at least four genes in the pathogenesis of AD. In early-onset familial AD mutations in the beta PP, S182 (presenilin 1) and STM2 (presenilin 2 or E5-1) genes have been found, while in the more common late-onset AD the presence of the apolipoprotein E4 isotype is a major risk factor. Genetic studies have also helped to elucidate the etiology of rarer cerebral amyloidoses such as the recently described Hungarian amyloidosis that is characterized by meningocerebrovascular amyloid deposition, with resultant dementia. This disease is linked to a mutation in the transthyretin gene. It is hoped that in the near future this increase in knowledge will allow the development of therapeutic approaches to slow the aging process.
衰老过程的一个重要组成部分是由基因决定的。关于衰老存在众多理论，其中许多都假定存在“长寿基因”。分子生物学和其他技术的最新进展使人们对衰老和与年龄相关的疾病有了更深入的了解。这将通过四种遗传性和散发性疾病来说明：阿尔茨海默病（AD）及相关病症、转甲状腺素蛋白痴呆症、冰岛型脑淀粉样血管病和瘙痒病相关疾病。阿尔茨海默病（AD）是这组疾病中最常见的，是西方国家痴呆症的主要病因。最近的基因和生化研究表明，至少有四个基因参与了AD的发病机制。在早发性家族性AD中，已发现β淀粉样前体蛋白（beta PP）、S182（早老素1）和STM2（早老素2或E5-1）基因发生突变，而在更常见的晚发性AD中，载脂蛋白E4亚型的存在是一个主要风险因素。基因研究也有助于阐明罕见脑淀粉样变性的病因，如最近描述的匈牙利淀粉样变性，其特征是脑膜脑血管淀粉样沉积，导致痴呆。这种疾病与转甲状腺素蛋白基因突变有关。希望在不久的将来，这种知识的增加将有助于开发延缓衰老过程的治疗方法。
