CORE--GENETICS

众所周知，遗传因素在阿尔茨海默病(AD)的发病机制中起重要作用。这是对导致早发性家族性AD(EOAD)的基因，即APP、PS1和PS2的最好理解。影响迟发性阿尔茨海默病(LOAD)发病年龄的单一遗传因素也被认为是载脂蛋白E。然而，我们对阿尔茨海默病的遗传学方面的理解仍然存在很大差距，包括影响发病年龄、外显性和EAOD和LOAD的表型表达的其他遗传因素。此外，很明显，许多其他类型的遗传性痴呆在临床、病理和分子上与阿尔茨海默病重叠，而且本身也很重要。UW ADRC Genetics Core的目的是提供独特的家庭材料和基因分型信息资源，以 合格的研究人员，以促进我们对阿尔茨海默病和其他痴呆疾病的遗传因素的了解。具体目标是：具体目标1：招募、鉴定、抽样和跟踪阿尔茨海默病和其他形式的痴呆症家庭。这些家族的表型数据和样本将提供给华盛顿大学ADRC的调查人员和华盛顿大学和其他机构的其他适当科学家。 具体目标2：为AD和其他痴呆的研究提供血清/血浆/DNA库。 具体目标3：为AD和痴呆研究提供基因分型和突变分析，包括(A)载脂蛋白(APOE)基因分型，(B)20个SNP位点的APOE单倍型分析，包括启动子多态性，以及(C)已知痴呆基因的突变筛查，包括早老素1和2(PSEN1，PSEN2)、普里昂基因(PRNP)、MAPT(tau基因)、α-突触核蛋白(ASN)、parkin和DJ-1。具体目标4：为新的痴呆基因和其他AD研究者发现的多态位点提供基因分型和突变分析。来自该核心的材料和信息将提供给UW ADRC内的合作者 威斯康星大学健康科学综合体以及美国和世界各地的所有其他相关调查人员。

Genetic factors are well-recognized to play an important role in the pathogenesis of Alzheimer's disease (AD). This is best unerstood for the genes causing early onset familial AD (EOAD), namely APP, PS1 and PS2. A single genetic factor influencing age of onset in late onset AD (LOAD) is also recognized, namely ApoE. Nevertheless, there still exist large gaps in our understanding of the genetic aspects of AD including additional genetic factors impacting age of onset, penetrance and phenotypic expression of both EAOD and LOAD. Furthermore, it is clear that many other types of hereditary dementia overlap clinically, pathologically and molecularly with AD, as well as being important in their own right. The purpose of the UW ADRC Genetics Core is to provide a unique resource of family material and genotyping information to qualified investigators to advance our understanding of genetic factors in AD and other dementing illnesses. The Specific Aims are: Specific Aim 1: To recruit, characterize, sample and follow families with Alzheimer's disease and other forms of dementia. Phenotypic data and samples from these families will be made available to investigators in the U W ADRC and other appropriate scientists at the University of Washington and other institutions. Specific Aim 2: Provide serum/plasma/DNA banking for studies of AD and other dementias. Specific Aim 3: Provide genotyping and mutational analysis for AD and dementia studies including (a) apolipoprotein (APOE) genotyping, (b) APOE haplotyping for 20 SNP sites including promoter polymorphisms and (c) mutation screening for known dementia genes including presenilins 1 and 2 (PSEN1,PSEN2), the prion gene (PRNP), MAPT (gene for tau), a-synuclein (ASN), parkin and DJ-1. Specific Aim 4: Provide genotyping and mutational anlysis for new dementia genes and polymorphic sites identified other AD investigators. Materials and information from this Core will be made available to collaborators within the UW ADRC, the UW Health Sciences Complex and all other relevant investigators in the US and worldwide.