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: 9978675
• 负责人: Brittany Nicole Dugger
• 金额: $ 85.93万
• 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/9978675
• 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; Hispanics; 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.

摘要：西班牙裔是美国增长最快的人口，流行病学数据表明他们是 患阿尔茨海默病的风险较高，脑血管疾病的发生率较高 （CVD）与非西班牙裔白人（NHW）相比。 AD 在神经病理学上的定义是： 神经原纤维缠结（NFT）和淀粉样斑块。除了这些特征之外，许多 AD 患者还存在多种症状： 神经病理学，包括路易体 (LB) 和 CVD 病理指标。研究，主要涉及 NHW 已表明这些神经病理学与临床、遗传和人口统计学变量之间的关联 提供对疾病机制和预防策略的见解。但相对缺乏 关于西班牙裔的神经病理学研究。必须对患有此病的个体进行神经病理学研究 多样化的特征，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 更加精准地制定预防措施。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） 并确定这种情况是否会因临床、遗传和人口统计变量而改变。提高效率 随着时间的推移和进一步的测量精度，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定量分析。根据之前的调查结果，我们的中心 假设是，与 NHW 相比，西班牙裔将有不同的神经病理学景观，而这些人 差异受到潜在危险因素的影响，尤其是心血管危险因素。我们的具体目标 目的是：1) 分析 NFT、斑块、LB 和病理学的存在、位置和半定量密度。 与 NHW 相比，西班牙裔 AD 患者的 CVD 指数，2) 分析并确定是否存在病理性 目标 1 的测量值会因临床、遗传和人口统计变量（APOE 状态、西班牙裔血统、 死亡年龄、脑血管事件（即中风）临床病史、高脂血症、糖尿病、高血压、性别、 和/或教育）以及 3）加强和调整深度学习流程以量化 AD 病理。我们将 利用伦敦大学三个阿尔茨海默病中心现有的特色资源 加州大学戴维斯分校、加州大学圣地亚哥分校和哥伦比亚大学进行了不同的尸检证实 AD 西班牙裔和 NHW 群体。此外，我们将使用加州大学圣保罗分校的机器学习资源 弗朗西斯科.该提案将是第一个描述 100 多个神经病理学的大规模倡议 墨西哥、波多黎各、古巴和多米尼加裔的西班牙裔人与 200 多名 NHW 进行比较，确定 共病风险因素的影响。分析神经病理学景观并了解潜在因素 有潜力揭示疾病发展的机制差异，从而实现更好的诊断， 治疗和预防策略。结果将直接促进对大脑健康（病理学）的理解 老年人口中一个重要且不断增长的部分，迄今为止，神经病理学信息仍然很少。