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

基本信息

批准号：
10680580
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
项目类别：
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/10680580
关键词：
African ancestry Age Alleles Alzheimer&apos s Disease Alzheimer&apos s disease blood test Alzheimer&apos s disease risk Alzheimer&apos 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 ancestry 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 American Ancestry Native Americans Neuropsychological Tests Nigerian Participant Patient Self-Report Patients Phosphorylation Plasma Play Population Prevalence Prevention Prevention strategy Probability Proteins Public Health Reporting Research Risk Role Sampling Surveys Telephone Test Result Testing Thinking Threonine Time Translating Tribes United States Universities Vascular Dementia Visit Work Writing behavioral neurology biobank blood-based biomarker brain health cerebral atrophy cigarette smoking demented dementia care dementia risk design epidemiologic data genetic risk factor health disparity high risk population improved informant neuroimaging neuron loss novel therapeutics personalized medicine prevent prospective racial population research clinical testing tau Proteins tau-1 treatment strategy tribal health virtual

项目摘要

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.

项目概要/摘要症状性阿尔茨海默病 (AD) 领域正在取得巨大进展。通过简单的血液测试诊断出的人均新痴呆症患者数量正在减少。旨在改善大脑健康的公共卫生运动正在出现，有望有效预防或治疗。虽然痴呆症诊断、预防和治疗方面的这些突破正在取得进展。值得庆祝的是，几乎不知道这些进步是否会转化为 Native 美国 (NA) 社区从生物医学角度对痴呆症知之甚少。例如，在撰写本文时，只有两个 NA 在 AD Neuroimaging 中拥有可用的血液检测数据 Initiative是美国最大的AD生物库，其中大约有200个NA被纳入其中。该国的 AD 联盟有超过 40,000 名参与者，缺乏有关 NA 痴呆症的知识。这是一个问题，预示着本已严重的健康差距将进一步扩大。假设美洲印第安人具有独特的痴呆症风险因素和 APOE ε4 的差异效应 – 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。排除使用 APOE ε4 进行“一刀切”的 AD 血液测试，当前项目的首要目标是确定北美部落民族中存在哪些类型的痴呆症，目前尚不清楚，但这是解决这一问题的第一步设计和实施有效的大脑健康政策第二个目标涉及测量祖先。 APOE 对 AD 风险和 AD 生物学的影响在 AD 血液测试中利用了 APOE 基因和 NA。直接定量与 AD 相关的有毒蛋白质以确定阳性或阴性结果。遗传自欧洲祖先，具有 APOE ε4 等位基因会增加 AD 的机会，并且增加 AD 血液检测结果呈阳性的可能性，但如果患者遗传了 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。 APOE ε4 和 AD 之间的中性关系可能适用于 NA – 我们小组的初步数据和其他人认为，从 NA 祖先继承 APOE ε4 基因同样不会增加 AD 风险。如果 NA 个体接受 AD 血液测试并携带 APOE ε4 等位基因，他们会接受改变生活的治疗吗？但对毁灭性病症的错误诊断因此我们的研究将衡量 APOE 之间的关系？由于 APOE 也是个性化医疗、风险/效益讨论的核心内容。对于抗淀粉样蛋白治疗、试验资格和基因引导治疗的目标，本研究将提供关于基于 APOE 的医学进步对 NA 的适用性的关键知识这是我们的第一项研究。试图将美洲印第安人痴呆症护理带入 21 世纪并提供为这一被研究群体受益于诊断、预防治疗方面的最新进展奠定了基础失智。