GENETIC EPIDEMIOLOGY OF ALZHEIMER DISEASE IN TWINS

描述：(改编自《调查人员摘要》)美国国家科学院 科学-国家研究理事会老年双胞胎退伍军人登记处 登记“)包含6,000对活生生的白人男性双胞胎，他们将会变老 一九九六至九七年度为68至80宗。这项广泛修订的申请建议在以下方面进行研究 登记处，加上迄今为止的工作，将产生130对双胞胎 患有阿尔茨海默病(AD)。这个以人口为基础的小组将使 继续研究三个主要目标：1)评估遗传 通过比较单合子(MZ)内起始片段的相似性来研究AD的病因 和双合子(DZ)配对，以及年龄匹配的无亲缘关系的配对 个人；2)环境对 阿尔茨海默病发病的可变性；(例如，在MZ内发病的可变性 对定义了环境影响可以达到的最大程度 修改AD的发病)；以及3)确定特定因素 与AD加速发作相关，使用同卵双胞胎对照方法。 这项研究将利用阿尔茨海默病遗传学的最新发展。 载脂蛋白E(APOE)基因座上的基因型影响这两种易感性 阿尔茨海默病及其发病时间。其他类似的基因系统可能很快就会出现 已确认身份。这样的发现使得能够将改进合并到 研究广泛(但异质性)基因的经典孪生范式 以及环境的影响。因此，调查人员表示，一个人可以 不仅在总体上估计AD的遗传度，而且还进行 用分割分析估计表型变异在 APOE或其他标记系统，因为这些被识别，以及仍然其他 (未知)易患阿尔茨海默病的基因。 几个MZ双胞胎对被描述为具有非常不同的 广告。因此，环境因素可能会改变发病，因此 一些遗传定义的阿尔茨海默病的人群风险。这项研究将 分析环境对发病变异性的贡献，并将 描述在基因匹配的集合中发病的差异 个人。它还将采用同孪生控制方法来寻求 可能导致这种变化的特定环境因素。 因为这里的AD病例通常会经历相对较早的 发病(考虑到他们的基因)，调查人员将专注于因素 加速阿尔茨海默病的发病。减少人口对这类物质的接触 各种因素可能导致公共卫生负担大幅下降 广告。 研究人员表示，以人口为基础的双胞胎设计仍然是 这类调查的理想方法，但这种调查的成本 学习是一个令人担忧的问题。他们进一步指出，当前的变化 与工作计划相比，工作计划导致预算减少19.2% 优先申请。

DESCRIPTION: (Adapted from Investigator's Abstract) The National Academy of Sciences - National Research Council Registry of aging twin veterans ("the Registry") contains 6,000 living pairs of white male twins who will be aged 68-80 in 1996-97. This extensively revised application proposes studies in the Registry that, combined with work to date, will yield 130 twin pairs with Alzheimer's disease (AD). That population-based panel will enable the continued investigation of three broad aims: 1) evaluation of genetic causes of AD by contrasting the similarity of onsets within monozygotic (MZ) and dizygotic (DZ) pairs, and within age-matched pairs of unrelated individuals; 2) characterization of the environmental contribution to variability of onset of AD; (for example, variability of onset within MZ pairs defines the maximum degree to which environmental influences can modify the onset of AD); and 3) identification of specific factors associated with accelerated onset of AD, using the co-twin control method. The research will capitalize upon recent developments in the genetics of AD. Genotype at the locus for apolipoprotein E (APOE) influences both liability to AD and its timing of onset. Other similar genetic systems may soon be identified. Such findings enable the incorporation of refinements into the classical twin paradigm of investigating broad (but heterogeneous) genetic and environmental influences. Thus, the investigators state that one can not only estimate the heritability of AD in general, but also undertake partitioned analyses to estimate the phenotypic variance to genotypes at APOE or other marker systems, as these are identified, and to still other (unknown) genes that predispose to AD. Several MZ twin pairs have been described with widely divergent onsets of AD. Environmental factors may therefore alter the onset, and hence the population risk, of some genetically defined forms of AD. This study will analyze the environmental contribution to variability of onset, and will characterize the divergence in onset within sets of genetically matched individuals. It will also employ the co-twin control method to seek the specific environmental factors that may be responsible for this variation. Because the AD cases here will typically have experienced a relatively early onset (given their genotype), the investigators will concentrate on factors that accelerate the onset of AD. Reduction in population exposure to such factors could result in a dramatic decrease in the public health burden of AD. The investigators state that a population-based twin design remains the ideal approach to these sorts of investigations, but the cost of such studies is a concern. They further state that alterations to the current work plan have resulted in a budget reduction of 19.2%, as compared wit the prior application.