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：
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
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/10525880
关键词：
African 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 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

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.

项目摘要/摘要痴呆症领域正在进行巨大进步。有症状的阿尔茨海默氏病（AD）可以是被诊断为简单的血液检查。人均新痴呆症患者的数量与公共卫生运动以改善大脑健康。新药正在出现，有效预防或治疗痴呆疾病。尽管这些突破性诊断，但预防和治疗是庆祝的原因，这些进步是否会转化为本地从生物医学的角度来看，美国（NA）社区对痴呆症的了解很少。为了实例，在撰写本文时只有两个NA在AD神经影像中具有可用的血液测试数据倡议是美国最大的广告生物库。大约有200个NA包括在最大的超过40,000名参与者中该国的广告财团。关于NA中痴呆症的知识不足是有问题的，预示着已经严重的健康差异的扩大。当前的研究中央假设是，美洲印第安人具有独特的痴呆危险因素和APOEε4 - 的差异作用 AD的最重要的遗传危险因素。这些因素将改变痴呆症的流行病学和使用APOEε4排除“一个尺寸适合所有尺寸” AD血液测试，当前项目的第一个目标是确定 NA部落国家存在着哪种类型的痴呆症，目前尚不清楚，但是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NA中APOE的依赖性影响。 AD血液测试利用APOE基因以及直接定量与AD相关的有毒蛋白，以确定阳性或阴性结果。如果从欧洲祖先继承，拥有APOEε4等位基因增加了AD的机会，也增加了增加了阳性AD血液测试结果的可能性。但是，如果患者从一个非洲祖先，对定义AD的有毒蛋白的积累产生了减弱的影响。相同 APOEε4与AD之间的中性关系可能适用于我们组的NA - 初步数据，其他人认为，同样，从Na祖先遗传APOEε4基因也不会增加AD的风险。如果NA个人接受AD血液测试并带有APOEε4等位基因，他们会收到改变生活的但是对于毁灭性疾病的错误诊断？因此，我们的研究将衡量APOE之间的关系 NA中的AD风险/生物学。由于Apoe还是个性化医学的核心，风险/福利讨论对于抗淀粉样疗法，试验资格和一般指导疗法的靶标，本研究将提供关于基于APOE的医疗进步对NA的适用性的批判性知识。这是我们的第一个研究试图将美洲印第安痴呆症护理带入21世纪并提供的知识这个理解的群体的基金会受益于诊断的最新进展，预防治疗失智。