Dementia prevalence, APOE, and blood-based biomarkers of AD in Native American communities

美洲原住民社区中痴呆症患病率、APOE 和 AD 血液生物标志物

• 批准号: 10525880
• 负责人: William G Mantyh
• 金额: $ 73.76万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-15 至 2027-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10525880
• 关键词: African; Age; Alleles; Alzheimer' s Disease; Alzheimer' s disease blood test; Alzheimer' s disease risk; Alzheimer' s disease therapy; Alzheimer’s disease biomarker; American; American Indians; Amyloid; Attenuated; Benefits and Risks; Biology; Blood Tests; Brain; Centers for Disease Control and Prevention (U.S.); Chippewa; Climacteric; Clinic; Cognitive; Communities; Country; Craniocerebral Trauma; Data; Dementia; Dementia with Lewy Bodies; Development; Diagnosis; Diagnostic; Eligibility Determination; Enrollment; Epidemiology; European; Evaluation; Foundations; Funding; Genes; Goals; Health Campaign; Health Policy; Heart Diseases; Homozygote; Impaired cognition; Incidence; Individual; Inherited; Institutional Review Boards; Japanese Population; Knowledge; Laboratories; Link; Magnetic Resonance Imaging; Measures; Medical; Memory; Minnesota; Native Americans; Neuropsychological Tests; Nigerian; Participant; Patient Self-Report; Patients; Plasma; Play; Population; Prevalence; Prevention; Prevention strategy; Probability; Proteins; Public Health; Race; Reporting; Research; Risk; Role; Sampling; Surveys; Telephone; Test Result; Testing; Therapy trial; Thinking; Threonine; Time; Translating; Tribes; United States; Vascular Dementia; Visit; Work; Writing; apolipoprotein E-4; base; behavioral neurology; biobank; blood-based biomarker; brain health; cerebral atrophy; cigarette smoking; dementia care; dementia risk; design; epidemiologic data; genetic risk factor; health disparity; high risk; improved; informant; neuroimaging; neuron loss; novel therapeutics; personalized medicine; prevent; prospective; research clinical testing; tau Proteins; tau mutation; tau-1; treatment strategy; tribal Nation; tribal college; tribal health; virtual

PROJECT SUMMARY/ABSTRACT Great advances are underway in the field of dementia. Symptomatic Alzheimer’s’ disease (AD) can be diagnosed with a simple blood test. The number of new dementia patients per capita is shrinking in parallel to public health campaigns to improve brain health. New drugs are emerging that promise to effectively prevent or treat dementing illness. While these breakthroughs in dementia diagnostics, prevention and treatment are cause for celebration, hardly anything is known about whether these advances will translate to Native American (NA) communities, where very little is known about dementia from a biomedical perspective. For instance, only two NA at the time of this writing have available blood test data in the AD Neuroimaging Initiative, the largest AD biobank in the United States. Approximately 200 NA have been included in the largest AD consortium in the country out of over 40,000 participants. This lack of knowledge regarding dementia in NA is problematic and portends a widening of already severe health disparities. The current study’s central hypothesis is that American Indians have unique dementia risk factors and a differential effect of APOE ε4 – the most significant genetic risk factor for AD. These factors will change the epidemiology of dementia and preclude a “one size fits all” AD blood test using APOE ε4, The first goal of the current project is to determine what types of dementia exist among NA Tribal Nations, which is currently unknown but is a first-step to designing and implementing effective brain health policy. The second goal involves measuring the ancestry- dependent effect of APOE on AD risk and AD biology in NA. AD blood tests utilize the APOE gene along with direct quantification of the toxic proteins associated with AD to determine a positive or negative result. If inherited from a European ancestor, having an APOE ε4 allele increases the chances of AD and also increases the probability of a positive AD blood test result. But if a patient inherits their APOE ε4 gene from an African ancestor, there is an attenuated impact on accumulation of toxic proteins that define AD. The same neutral relationship between APOE ε4 and AD likely applies to NA – preliminary data from our group and others suggest that inheriting an APOE ε4 gene from a NA ancestor similarly does not increase the risk of AD. If an NA individual undergoes an AD blood test and carries an APOE ε4 allele, will they receive a life-changing but false diagnosis for a devastating condition? Our study thus will measure the relationship between APOE and AD risk/biology in NA. As APOE is also a centerpiece of personalized medicine, risk/benefit discussions for anti-amyloid therapy, trial eligibility, and the target of genetically guided therapies, this study will provide critical knowledge about the applicability of APOE based medical advances to NA. This is the first study to our knowledge that attempts to bring American Indian dementia care into the 21st century and provide a foundation for this understudied group to benefit from the latest advances in diagnosis, prevention treatment of dementia.

项目总结/摘要 痴呆症领域正在取得巨大进展。阿尔茨海默病（AD）的症状可以是 一个简单的血液测试就能确诊人均新痴呆症患者人数正在减少， 公共卫生运动，以改善大脑健康。新的药物正在出现，有望有效地预防或 治疗痴呆症虽然这些在痴呆症诊断、预防和治疗方面的突破， 值得庆祝的是，几乎没有什么是知道这些进步是否会转化为本土 美国（NA）社区，从生物医学的角度对痴呆症知之甚少。为 例如，在撰写本文时，只有两个NA在AD神经成像中有可用的血液测试数据 这是美国最大的AD生物库。大约200名NA已被纳入最大的 AD财团在该国的40 000多名参与者中。这种缺乏知识的痴呆症在NA 这是一个问题，预示着本已严重的健康差距正在扩大。目前的研究主要 一种假说认为，美洲印第安人具有独特的痴呆风险因素，APOE ε4 - AD最重要的遗传风险因素。这些因素将改变痴呆症的流行病学， 排除“一刀切”的AD血液检测使用APOE ε4，目前项目的第一个目标是确定 NA部落民族中存在哪些类型的痴呆症，目前尚不清楚，但这是第一步， 制定和实施有效的脑健康政策。第二个目标是测量祖先- 在NA中APOE对AD风险和AD生物学的依赖性作用。AD血液测试利用APOE基因沿着 直接定量与AD相关的毒性蛋白以确定阳性或阴性结果。如果 遗传自欧洲祖先，具有APOE ε4等位基因增加AD的机会， 增加了AD血液检测结果阳性的可能性。但是如果患者从一个人那里遗传了他们的APOE ε4基因， 非洲祖先，对定义AD的有毒蛋白质的积累有减弱的影响。相同的 APOE ε4和AD之间的中性关系可能适用于NA -来自我们小组的初步数据， 其他人认为从NA祖先遗传APOE ε4基因同样不会增加AD的风险。 如果一个NA个体接受AD血液检测并携带APOE ε4等位基因，他们会接受改变生活的治疗吗？ 但对一种致命疾病的错误诊断因此，我们的研究将测量载脂蛋白E与 和AD风险/生物学在NA。由于APOE也是个性化医疗的核心，风险/获益讨论 对于抗淀粉样蛋白治疗、试验合格性和遗传指导治疗的靶点，本研究将提供 关于APOE基础医学进展对NA的适用性的关键知识。这是我们第一次研究 知识，试图把美国印第安人痴呆症护理到21世纪世纪，并提供一个 为这一未充分研究的群体奠定了基础，使其受益于诊断、预防和治疗方面的最新进展， 痴呆