AD Biomarkers and Endothelial Dysfunction in Caucasians and African Americans

非洲裔美国人约占美国人口的10%，但在生物标志物- 与衰老相关的研究，如阿尔茨海默病神经成像倡议(ADNI)和全球ADNI。 流行病学研究表明，与非西班牙裔白人(NHW)相比，非裔美国人 更有可能发展为轻度认知障碍(MCI)和阿尔茨海默病(AD)，但速度可能较慢 认知和功能衰退的比率。这些都表明存在MCI/AD的内表型 非裔美国人，但没有现代化学或成像生物标记物的流行病学研究不能 区分这些观察的可能解释，包括血管共同病理，AD 内表型和神经保护性抗炎机制。通过NIA资助的R21(AG043885， Pi：Hu)，我们已经开始了一项关于种族依赖和种族独立相关因素的横断面研究 非裔美国人和非裔美国人之间AD生物标志物分布的差异。在项目1中，我们提出了一个 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 对150个横断面队列进行纵向生物标志物分析，并将队列扩大100个 新的受试者解释了更多可能影响AD进展速度的因素。我们会直接 检查1)生物标志物确认的阿尔茨海默病患者的认知功能减退率在非裔美国人之间是否存在差异 和nhw，2)非裔美国人和nhw的内皮功能障碍经历了纵向变化，以及3) 阿尔茨海默病与内皮功能障碍之间的相互作用是通过神经炎症介导的。在目标1中，我们 将确定具有AD生物标志物特征(脑脊液、核磁共振)的非裔美国人受试者是否经历认知减慢 比具有相同AD生物标志物轮廓的NHW受试者下降。在目标2中，我们将确定非洲人是否 美国受试者在内皮功能障碍方面比NHW受试者经历更大的纵向变化。 新型内皮标记物的脑脊液水平及脑血流量、轴突完整性和脑组织的MRI分析 微出血。在目标3中，我们将对纵向AD和内皮标记物之间的相互作用进行建模， 并测试这一假设，即具有AD生物标记物特征的非裔美国人更有可能患有 与具有相同AD生物标志物图谱的NHW受试者相比，抗炎脑脊液图谱。成功完成 这些目标将创建一个现代的生物标志物丰富的数据集，由同等比例的非裔美国人组成 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，确定脑脊液和MRI AD生物标记物的纵向变化是否不同 ，并为一项多中心、多模式的生物标志物研究奠定了基础 非裔美国人和nhw高年级学生。

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.