The Contribution of the Oral Microbiome to Alzheimer’s Disease Risk

口腔微生物群对阿尔茨海默病风险的影响

• 批准号: 10719255
• 负责人: Irene Yang
• 金额: $ 79.43万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-12 至 2028-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10719255
• 关键词: Address; Adult; Affect; Age; Alleles; Alzheimer disease prevention; Alzheimer' s Disease; Alzheimer' s disease related dementia; Alzheimer' s disease risk; Alzheimer’s disease biomarker; American; Amyloid beta-42; Bacteria; Behavior; Biological Markers; Biometry; Blood; Candida albicans; Cerebrospinal Fluid; Chronic; Clinical; Cognitive; Culture-independent methods; Data; Dentistry; Development; Diagnosis; Diagnostic; Disease; Disease Marker; Disease Progression; Education; Elderly; Enrollment; Epidemiology; Ethnic Population; Etiology; Exposure to; Family; Family history of; Feasibility Studies; Forsythia; Funding; Fusobacterium nucleatum; Future; Genetic; Gingiva; Goals; Health; Human; Hygiene; Individual; Inequity; Infection; Inflammation; Inflammatory; Intervention; Interview; Investigation; Knowledge; Life Style; Link; Longitudinal cohort study; Medical; Microbial Biofilms; Neuropsychological Tests; Onset of illness; Oral; Oral Characters; Oral Examination; Oral Microbiology; Oral cavity; Oral health; Organism; Participant; Pathogenesis; Pathway interactions; Periodontal Diseases; Periodontium; Peripheral; Pharmaceutical Preparations; Porphyromonas gingivalis; Quality of life; Recording of previous events; Research; Risk; Risk Factors; Role; Saliva; Salivary; Sampling; Societies; Structure; Surveys; Symptoms; Taxonomy; Time; Tissues; Tooth structure; Treponema denticola; United States National Institutes of Health; Viral; Virus; Visit; apolipoprotein E-4; clinical examination; clinically relevant; cohort; fungus; health care availability; high risk; inflammatory marker; interest; microbiome; microbiota; middle age; modifiable risk; multidisciplinary; neuroinflammation; novel; oral bacteria; oral condition; oral microbiome; oral spirochetes; periopathogen; prevent; racial diversity; racial population; sample collection; social; social determinants; social health determinants; systemic inflammatory response; tau Proteins; tau-1

Abstract Alzheimer’s disease (AD) affects 6.5 million Americans inflicting tremendous burden on our society both economically and in terms of human suffering, yet the etiology of AD is not fully understood. Risk factors for AD are numerous and include demographic, genetic, lifestyle, medical, environmental, psychiatric, and infectious factors. Among the infectious factors known to be associated with AD is periodontal disease (PerioD). PerioD is a polymicrobial infection of the gingival tissue and one of the most common conditions of the oral cavity. There is a growing interest in the connection between PerioD and AD, yet the mechanism between underlying this association is unknown, and most studies have focused their investigation on a limited number of PerioD- associated organisms, for example Porphyromonas gingivalis, Tanerella forsythia, and Treponema denticola. Currently, a major and fundamental obstacle in the field is the lack of a cross-kingdom (bacterial, viral, fungal), comprehensive characterization of the oral microbiome of PerioD as it relates to AD risk. The overall purpose of the proposed project is to investigate the clinical relevance of the oral microbiome in individuals most at risk for AD. 150 middle aged individuals will be enrolled in this longitudinal cohort study. The main objective is to characterize the taxonomy and function of oral bacteria, viruses and fungi among cognitively normal individuals at risk for AD, and over a two-year period, investigate relationships among PerioD-associated microbiome features, inflammation, social determinants of oral health, and AD CSF biomarkers (Aβ42, total-Tau, and phospho-Tau). We will leverage existing NIH funded, well-characterized cohorts that include racially diverse individuals at high risk for AD (through family history or APOE4 allele). Participants will complete 3 study visits annually. Cerebral spinal fluid for AD and inflammatory markers will be collected at baseline and Yr2. Annual assessments and specimen collection will include: a clinical oral examination; subgingival plaque for microbiome assessment; saliva for inflammatory markers; blood for systemic inflammatory markers; neuropsychological testing; and surveys (medication/health history; oral symptoms, hygiene behavior, and quality of life; social determinants of health). Finally, we will conduct semi-structured in-depth interviews to explore the social determinant factors related to oral health and AD. Generated data will inform larger NIH funded studies and, to our knowledge, provide the largest and most comprehensive characterization of the oral microbiome in a racially diverse sample of individuals at risk for AD.

抽象的 阿尔茨海默氏病（AD）影响了650万美国人，对我们的社会造成了巨大的伯宁 从经济上讲，就人类的痛苦而言，AD的病因尚未完全理解。广告的风险因素 很多，包括人口统计，遗传，生活方式，医学，环境，精神病和感染力 因素。已知与AD相关的传染性因素包括牙周疾病（周期）。 是牙龈组织的多数感染，也是口腔最常见的条件之一。 对时期和广告之间的联系越来越感兴趣，但是基础之间的机制 该关联尚不清楚，大多数研究都将调查集中在有限数量的时期 - 相关的生物，例如牙龈卟啉单胞菌，坦纳氏菌和treponema denticola。 目前，该领域的一个主要且基本的障碍是缺乏跨王朝（细菌，病毒，真菌）， 与AD风险有关的时期口腔微生物组的全面表征。总体目的 拟议的项目是调查口腔微生物组对最有风险的个体的临床相关性 对于广告。这项纵向队列研究将入学150名中年人。主要目标是 表征认知正常个体中口腔细菌，病毒和真菌的分类学和功能 有AD的风险，并在两年的时间内研究了与周期相关的微生物组之间的关系 特征，感染，口腔健康的社会决定者以及AD CSF生物标志物（Aβ42，Total-Tau和 磷酸tau）。我们将利用现有的NIH资助，特征良好的队列，包括种族潜水员 AD高风险的个人（通过家族史或APOE4等位基因）。参与者将完成3次学习访问 每年。将在基线和YR2时收集用于AD和炎症标记的脑脊髓液。年度的 评估和标本收集将包括：临床口腔检查； subgingival牌匾 微生物组评估；用于炎症标记的唾液；全身性炎症标记的血液； 神经心理学测试；和调查（药物/健康病史；口腔症状，卫生行为和 生活质量；健康的社会决定者）。最后，我们将进行半结构化的深入访谈 探索与口腔健康和广告有关的社会确定因素。生成的数据将告知更大的NIH 据我们所知，资助的研究提供了口头最大，最全面的特征 在大致多样化的AD风险的个体样本中的微生物组。