ASSOCIATION BETWEEN APOE AND AGE OF ONSET IN ALZHEIMER?S DISEASE

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 背景资料：载脂蛋白E（ApoE）基因型是阿尔茨海默病发病年龄的重要危险因素和调节因子;最近的研究表明ApoE-e4等位基因与晚发性阿尔茨海默病（LOAD）相关;本研究旨在探讨ApoE-e4等位基因与EOAD和LOAD患者皮质萎缩和海马体积的关系，使用皮层模式匹配（CPM）算法和海马放射状映射（HRM）。 研究方法：将临床严重程度相似的EOAD和LOAD患者的高分辨率3D MR图像与年龄和性别匹配的对照进行比较。CPM用于识别病例与对照组皮质灰质密度不同的区域，HRM用于评估海马体积差异。 使用12参数线性变换将MR图像标准化为定制模板，并提取两个半球的3D皮质表面;在每个半球的外侧和内侧表面上手动勾勒出29个脑沟，并绘制额外的3D线以界定半球间回界限。创建群体特定模板，对受试者之间的追踪的脑沟进行平均，并且脑沟用作界标以将每个受试者的解剖结构扭曲到模板。原始MR图像被分割成灰质、白色物质和CSF，并且将用皮质模式匹配获得的翘曲场应用于GM图像，从而允许在数千个同源皮质位置处测量GM。计算每组的平均灰质比例，并计算显示灰质密度与组之间相关性的统计学显著性图（apoE 4携带者中的EOAD与LOAD，非携带者中的EOAD与LOAD，携带者与非携带者）。 在将原始MRI配准到立体定向空间后，通过在35个冠状切片上手动追踪海马本体和海马下托的轮廓来分离海马结构;中间曲线将自动定义为每个图像切片中海马边界质心所描绘的3D曲线。通过自动测量从表面点到为个体海马表面模型定义的中间曲线的径向3D距离，评估每个边界点处每个海马的径向尺寸。较短的径向距离将用作萎缩的指标;将生成统计图，表明径向海马距离的局部组差异。 预期成果。在EOAD患者中，ApoE可能与更大的皮质萎缩相关，在LOAD患者中，ApoE可能与更大的海马萎缩相关。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Background: The apolipoprotein E (ApoE) genotype is a significant risk factor and modulator of age of onset in Alzheimer's disease; recent studies showed an association between ApoE-e4 allele and late onset Alzheimer disease (LOAD); less is known about possible ApoE-e4 allele effects in early-onset (EOAD); here we aim to investigate the association of ApoE-e4 allele on cortical atrophy and hippocampal volumes in EOAD and LOAD patients, using cortical pattern matching (CPM) algorithms and hippocampal radial mapping (HRM). Methods: High-resolution 3D MR images of EOAD and LOAD patients of similar clinical severity will be compared to those of age- and sex-matched controls. CPM is used to identify regions where the cortical gray matter density differs in cases vs controls, and HRM to assess hippocampal volumes difference. MR images are normalized to a customized template using a 12 parameter linear transformation and 3D cortical surfaces of both hemispheres are extracted; 29 sulci are manually outlined on the lateral and medial surface of each hemisphere, and additional 3D lines are drawn to delimit interhemispheric gyral limits. A population specific templates is created averaging the traced sulci among subjects, and the sulci are used as landmarks to warp each subject's anatomy to the template. Original MR images are segmented into gray matter, white matter, and CSF, and the warping fields obtained with cortical pattern matching is applied to the GM images, thus allowing measurement of GM at thousands of homologous cortical locations. The mean gray matter proportion is computed for each group, and statistical significance maps showing correlation between gray matter density and group (EOAD vs LOAD in apoE4 carriers, EOAD vs LOAD in noncarriers, carriers vs non-carriers) will be computed. The hippocampal formation will be isolated by manually tracing on 35 coronal slices the outlines of the hippocampus proper and subiculum after registration of original MRI to stereotactic space; a medial curve will be automatically defined as the 3D curve traced out by the centroid of the hippocampal boundary in each image slice. The radial size of each hippocampus at each boundary point will be assessed by automatically measuring the radial 3D distance from the surface points to the medial curve defined for individual's hippocampal surface model. Shorter radial distances will be used as an index of atrophy; statistical maps will be generated indicating local group differences in radial hippocampal distance. Expected results. ApoE could be associated with greater cortical atrophy in EOAD patients, and with greater hippocampal atrophy in LOAD.