GENETICS, MORTALITY AND DEMENTIA IN DOWN SYNDROME

唐氏综合症的遗传学、死亡率和痴呆症

• 批准号: 2825097
• 负责人: WARREN B ZIGMAN
• 金额: $ 36.16万
• 依托单位: INSTITUTE FOR BASIC RES IN DEV DISABIL
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-02-16 至 2004-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2825097
• 关键词: Alzheimer's disease; Downs syndrome; age difference; aging; amyloid proteins; apolipoprotein E; behavior test; cell line; chromosome translocation; clinical research; dementia; fluorescent in situ hybridization; genetic markers; genetic susceptibility; genotype; human middle age (35-64); human mortality; human old age (65+); human subject; karyotype; long term survivor; phenotype; premature aging

Down syndrome, one of the most common genetic causes of mental retardation associated with genetic factors, occurs in approximately 1.2 per 1000 live births, is typically caused by a nondisjunction of the 21st chromosome during meiosis resulting in a complete trisomy genotype, although atypical forms occur occasionally. Adults with Down syndrome have benefited from the advances in public health practices that have resulted in a dramatic extension in life expectancy. However, Down syndrome is still characterized by increased mortality rates during later stages of life. Causes of higher mortality rates later in life may be due to a number of factors, two of which are an increased risk for Alzheimer~s disease and an apparent tendency toward premature aging. Aging processes among adults with Down syndrome have been of interest for over 100 years because of the occurrence of the signs and symptoms of Alzheimer~s disease in the population. Indeed, brain tissue of virtually all adults with Down syndrome over 35 to 40 years of age displays significant accumulations of amyloid plaques, historically considered to be a hallmark of Alzheimer's disease neuropathology presumably due to the triplication and over expression of the gene for beta-amyloid precursor protein located on chromosome 21. The genotypic and phenotypic characteristics of the "oldest old" (i.e., 65 and older) adult population with mental retardation due to Down syndrome will be compared to those of their younger peers (also with Down syndrome) in order to identify genetic risk factors associated with survival and the cognitive declines associated with dementia of the Alzheimer~s-type. We have been able to identify a group of 100 people with Down syndrome 65 years of age or older. Investigation of this unique group of individualist will allow us to characterize the phenotype of the ~oldest old~ with Down syndrome and identify genetic and health status factors that are associated with extended survival and successful aging on one hand and the development of DAT on the other.

唐氏综合症是心理的最常见遗传原因之一 与遗传因素相关的迟钝，大约发生 每1000个活产1.2，通常是由非分离引起的 减数分裂过程中的第21颗染色体导致完整的三体染色体 基因型，尽管非典型形式偶尔发生。 成年人 唐氏综合症从公共卫生的进步中受益 实践导致了生命的巨大延长 期待。 但是，唐氏综合症仍然以 生命后期的死亡率提高。 原因 较高的死亡率以后可能是由于许多 因素，其中两个是阿尔茨海默氏病的风险增加 以及明显的过早衰老的趋势。 衰老过程 在唐氏综合症的成年人中，人们对100多个感兴趣 由于发生的体征和症状的发生 人群中的阿尔茨海默氏病。 确实，脑组织 几乎所有患有35至40岁以上唐氏综合症的成年人 在历史上显示淀粉样蛋白斑块的大量积累 被认为是阿尔茨海默氏病神经病理学的标志 大概是由于基因的三倍和表达 对于位于染色体21的β-淀粉样蛋白前体蛋白。 “最古老的旧”的基因型和表型特征（即 65岁及以上）由于下降而患有智力低下的成年人口 将综合征与年轻同龄人的综合症进行比较（也将与 唐氏综合症）为了识别相关的遗传危险因素 随着生存和与痴呆相关的认知下降 阿尔茨海默氏症〜S型。 我们已经能够识别一组100组 唐氏综合症患者65岁或以上。 调查 这个独特的个人主义者将使我们能够表征 〜老〜与唐氏综合症的表型，并识别遗传 与延长生存有关的健康状况因素 一方面，成功的衰老和DAT的发展 其他。