AD Biomarkers and Endothelial Dysfunction in Caucasians and African Americans

非洲裔美国人占美国人口的10%左右，但在生物标志物中的代表性不足- 相关的老化研究，如阿尔茨海默病神经成像倡议（ADNI）和世界范围的ADNI。 流行病学研究表明，与非西班牙裔白色（NHW）美国人相比，非洲裔美国人 更有可能发展为轻度认知障碍（MCI）和阿尔茨海默病（AD），但可能有较慢的 认知和功能下降的速度。这些表明MCI/AD内表型的存在， 非洲裔美国人，但没有现代化学或成像生物标志物的流行病学研究不能 区分这些观察结果的潜在解释，包括血管共病，AD 内表型和神经保护性抗炎机制。通过NIA资助的R21（AG 043885， PI：Hu），我们已经开始了一项关于种族相关和种族无关因素的横断面研究， 非裔美国人和NHW之间AD生物标志物谱的差异。在项目1中，我们提出了一个 一项纵向、多模式生物标志物研究，以检查两者之间的AD进展率是否存在差异 由于内皮功能障碍、神经炎症或真正的AD内表型而导致的种族。我们将招募 150人的横断面队列进行纵向生物标志物分析，并将队列扩大100人 新的受试者，以解释更多可能影响AD进展率的因素。我们会直接 检查1）非裔美国人之间经生物标志物证实的AD病例的认知下降率是否不同 2）内皮功能障碍在非裔美国人和NHW中经历纵向变化，以及3） AD和内皮功能障碍之间的相互作用通过神经炎症介导。目标1： 将确定具有AD生物标志物特征（CSF、MRI）的非裔美国人受试者是否发生认知功能减退 与具有相同AD生物标志物特征的NHW受试者相比下降。目标2：确定非洲 美国受试者比NHW受试者经历更大的内皮功能障碍的纵向变化，使用 CSF中新型内皮标记物的水平和脑血流、轴突完整性和脑血管病的MRI分析 微出血在目标3中，我们将模拟纵向AD和内皮标志物谱之间的相互作用， 并检验假设，即具有AD生物标志物特征的非裔美国人受试者更有可能患有AD。 与具有相同AD生物标志物特征的NHW受试者相比，NHW受试者的抗炎CSF特征更显著。成功完成 这些目标将创建一个现代生物标志物丰富的数据集，包括同等比例的非洲裔美国人， 和NHW老年人，构建了非洲现代AD和内皮标志物的第一个进展概况， 美国老年人，确定CSF和MRI AD生物标志物的纵向变化是否与 非裔美国人和NHW，并为多中心，多模式生物标志物研究奠定了基础， 非裔美国人和NHW老年人。

African Americans represent about 10% of the population in the US, but are under-represented in biomarker- related aging studies such as the Alzheimer's Disease Neuro-imaging Initiative (ADNI) and World Wide ADNI. Epidemiologic studies show that, compared to non-Hispanic white (NHW) Americans, African Americans are more likely to develop mild cognitive impairment (MCI) and Alzheimer's disease (AD), but may have slower rates of cognitive and functional decline. These point to the existence of an MCI/AD endophenotype for African Americans, but epidemiological studies without modern chemical or imaging biomarkers cannot differentiate between potential explanations for these observations, including vascular co-pathology, AD endophenotype, and neuroprotective anti-inflammatory mechanisms. Through a NIA-funded R21 (AG043885, PI: Hu), we have begun a cross-sectional study on race-dependent and race-independent factors associated with differences in AD biomarker profile between African Americans and NHW. In Project 1, we propose a longitudinal, multi-modal biomarker study to examine whether AD progression rates differ between the two races because of endothelial dysfunction, neuro-inflammation, or a true AD endophenotype. We will recruit the cross sectional cohort of 150 to undergo longitudinal biomarker analysis, and expand the cohort by 100 new subjects to account for more factors which may influence rates of AD progression. We will directly examine if 1) rates of cognitive decline in biomarker-confirmed cases of AD differ between African Americans and NHW, 2) endothelial dysfunction undergoes longitudinal change in African Americans and NHW, and 3) the interaction between AD and endothelial dysfunction is mediated through neuro-inflammation. In Aim 1, we will determine if African Americans subjects with AD biomarker profiles (CSF, MRI) experience slower cognitive decline than NHW subjects with the same AD biomarker profiles. In Aim 2, we will determine if African Americans subjects undergo greater longitudinal change in endothelial dysfunction than NHW subjects, using CSF levels of novel endothelial markers and MRI analysis of cerebral blood flow, axonal integrity, and cerebral microbleeds. In Aim 3, we will model the interaction between longitudinal AD and endothelial marker profiles, and test the hypothesis that African Americans subjects with AD biomarker profiles are more likely to have an anti-inflammatory CSF profile than NHW subjects with the same AD biomarker profiles. Successful completion of these aims will create a modern biomarker-rich dataset consisting of equal proportions of African Americans and NHW seniors, construct the first progression profiles of modern AD and endothelial markers in African Americans seniors, identify whether longitudinal changes in CSF and MRI AD biomarkers differ between African Americans and NHW, and set the stage for a multi-center, multi-modal biomarker study involving African Americans and NHW seniors.