The Neuropathologic Landscape of Alzheimer's Disease in Hispanic Decedents

西班牙裔死者阿尔茨海默病的神经病理学景观

• 批准号: 10386888
• 负责人: Brittany Nicole Dugger
• 金额: $ 95.91万
• 依托单位: UNIVERSITY OF CALIFORNIA AT DAVIS
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-08-01 至 2024-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10386888
• 关键词: Adult; Affect; Age; Alzheimer' s Disease; Alzheimer' s disease pathology; Alzheimer' s disease patient; Anatomy; Autopsy; Brain; Brain region; California; Cerebrovascular Disorders; Cessation of life; Characteristics; Clinical; Complement; Computer Vision Systems; Consumption; Cuban; Data; Dementia; Demographic Factors; Deposition; Development; Diabetes Mellitus; Diagnosis; Disease; Dominican; Education; Elderly; Evaluation; Event; Frequencies; Genetic; Glean; Goals; Heterogeneity; Hispanic; Hispanic Populations; Human; Hyperlipidemia; Hypertension; Individual; Knowledge; Lewy Bodies; Light; Location; Machine Learning; Measurement; Measures; Medical Genetics; Methods; Mexican; Neurofibrillary Tangles; Not Hispanic or Latino; Pathologic; Pathology; Phase; Phenotype; Population; Prevention strategy; Preventive measure; Puerto Rican; Recording of previous events; Research; Resources; Risk Factors; San Francisco; Senile Plaques; Specificity; Statistical sensitivity; Stroke; System; Techniques; Temporal Lobe; Testing; Time; Universities; base; brain health; cardiovascular disorder risk; cardiovascular risk factor; cerebrovascular; clinical practice; cohort; comorbidity; deep learning; dementia risk; density; disorder risk; epidemiologic data; high risk; indexing; innovation; insight; machine learning algorithm; neuropathology; protective factors; sex; social culture; tool; treatment strategy

Abstract: Hispanics are the fastest growing population in the US and epidemiological data suggests they are at a higher risk of developing Alzheimer’s disease and have a higher occurrence of cerebrovascular disease (CVD) when compared to non-Hispanic Whites (NHWs). AD is defined neuropathologically by the deposition of neurofibrillary tangles (NFTs) and amyloid plaques. In addition to these hallmarks, many AD patients have mixed neuropathologies, including Lewy bodies (LBs) and pathological indices of CVD. Studies, involving mainly NHWs, have shown associations of these neuropathologies with clinical, genetic, and demographic variables providing insights into disease mechanisms and prevention strategies. However, there is a relative dearth of neuropathology studies on Hispanics. It is imperative to have neuropathology studies with individuals having diverse characteristics as this maximizes variability allowing for better identification of disease risk factors for more precision in development of preventative measures. This study will examine the neuropathologic landscape (the presence, location, and density of NFTs, plaques, CVD and LBs) of Hispanics compared to NHWs and determine if this landscape is altered by clinical, genetic, and demographic variables. To achieve efficiencies in time and further measurement precision we will enhance and adapt innovative machine learning algorithms to narrow in on pathology location and provide more quantitative analyses. Based on previous findings our central hypothesis is that Hispanics will have different neuropathologic landscapes when compared to NHWs and these differences are influenced by underlying risk factors, especially cardiovascular risk factors. Our specific aims are to: 1) profile the presence, location, and semi-quantitative densities of NFTs, plaques, LBs, and pathological indices of CVD in the setting of AD in Hispanics compared to NHWs, 2) profile and determine if pathologic measures from Aim 1 are altered by clinical, genetic, and demographic variables (APOE status, Hispanic origin, age at death, clinical history of cerebrovascular events (i.e. stroke), hyperlipidemia, diabetes, hypertension, sex, and/or education) and 3) strengthen and adapt a deep learning pipeline for quantifying AD pathologies. We will capitalize on existing well-characterized resources within three Alzheimer’s disease centers at University of California- Davis, the University of California- San Diego, and Columbia that contain a diverse autopsy confirmed AD Hispanic and NHW cohort. Also, we will use machine learning resources at the University of California San Francisco. This proposal will be the first largescale initiative to delineate the neuropathology in over 100 Hispanics of Mexican, Puerto Rican, Cuban, and Dominican origins compare to over 200 NHWs and determine the impact of comorbid risk factors. Profiling neuropathologic landscapes and understanding underlying factors has potential to shed light on mechanistic differences in disease development leading to better diagnosis, treatment, and prevention strategies. Results will directly advance understanding of brain health (pathology) in an important and growing part of the elderly population that to date there is miniscule neuropathology information.

翻译后摘要：西班牙裔是美国增长最快的人口和流行病学数据表明，他们是 患老年痴呆症的风险更高，脑血管疾病的发生率更高 (CVD)与非西班牙裔白人（NHWs）相比。AD在神经病理学上被定义为 神经纤维缠结（NFT）和淀粉样斑块。除了这些特征外，许多AD患者还患有混合型AD。 神经病理学，包括路易体（LB）和CVD的病理学指标。研究，主要涉及 NHWs已经显示出这些神经病理学与临床、遗传和人口统计学变量的相关性 深入了解疾病机制和预防策略。然而，相对缺乏 神经病理学研究必须对患有以下疾病的个体进行神经病理学研究 不同的特征，因为这最大限度地提高了变异性，从而可以更好地识别疾病风险因素， 在制定预防措施方面更加精确。这项研究将检查神经病理学 与NHW相比，西班牙裔的景观（NFT、斑块、CVD和LB的存在、位置和密度） 并确定这一景观是否被临床、遗传和人口统计学变量所改变。实现效率 在时间和更高的测量精度方面，我们将增强和调整创新的机器学习算法， 缩小病理位置并提供更多的定量分析。根据先前的研究结果，我们的中心 假设是，西班牙裔将有不同的神经病理景观相比，NHW和这些 差异受到潜在风险因素，特别是心血管风险因素的影响。我们的具体目标 1）分析NFT、斑块、LB和病理性斑块的存在、位置和半定量密度， 与NHW相比，西班牙裔AD背景下的CVD指数，2）特征并确定病理 来自目标1的测量被临床、遗传和人口统计学变量（APOE状态，西班牙裔， 死亡时的年龄、脑血管事件（即中风）的临床病史、高脂血症、糖尿病、高血压、性别， 和/或教育）和3）加强和调整用于量化AD病理的深度学习管道。我们将 利用现有的特点鲜明的资源在三个阿尔茨海默病中心在大学 加州-戴维斯，加州-圣地亚哥大学，和哥伦比亚，包含一个不同的尸检确认 AD西班牙裔和NHW队列。此外，我们将使用加州大学旧金山分校的机器学习资源， 弗朗西斯科。这项提案将是第一个大规模的倡议，以描绘神经病理学在100多个 墨西哥，波多黎各，古巴和多米尼加血统的西班牙裔人与200多名NHW进行比较，并确定 共病危险因素的影响。描绘神经病理学景观并了解潜在因素 有可能揭示疾病发展的机制差异，从而更好地诊断， 治疗和预防策略。研究结果将直接促进对大脑健康（病理学）的理解， 这是老年人口中重要且不断增长的一部分，迄今为止，神经病理学信息极少。