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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.

项目总结/文摘