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 阿尔茨海默病 (AD) 影响着 650 万美国人，给我们的社会带来巨大负担 尽管从经济角度和人类痛苦角度来看，AD 的病因尚未完全明了。 AD 的危险因素 数量众多，包括人口、遗传、生活方式、医学、环境、精神和传染病 因素。已知与 AD 相关的感染因素之一是牙周病 (PerioD)。时期 是牙龈组织的多种微生物感染，也是最常见的口腔疾病之一。 人们对 PerioD 和 AD 之间的联系越来越感兴趣，但底层之间的机制 这种关联是未知的，大多数研究都将调查集中在有限数量的 PerioD- 相关生物体，例如牙龈卟啉单胞菌、连翘塔内菌和齿垢密螺旋体。 目前，该领域的一个主要和根本障碍是缺乏跨界（细菌、病毒、真菌）、 PerioD 口腔微生物组的综合表征，因为它与 AD 风险相关。总体目的 拟议项目的目的是调查口腔微生物组在高危个体中的临床相关性 对于AD。 150 名中年人将被纳入这项纵向队列研究。主要目标是 描述认知正常个体口腔细菌、病毒和真菌的分类和功能 有 AD 风险的人，在两年的时间内，调查 PerioD 相关微生物组之间的关系 特征、炎症、口腔健康的社会决定因素和 AD CSF 生物标志物（Aβ42、总 Tau 和 磷酸-Tau)。我们将利用现有的 NIH 资助的、特征鲜明的队列，其中包括不同种族的人 AD 高危人群（通过家族史或 APOE4 等位基因）。参与者将完成 3 次考察访问 每年。将在基线和第二年收集 AD 脑脊液和炎症标记物。年度的 评估和样本采集将包括： 临床口腔检查；龈下菌斑 微生物组评估；唾液中的炎症标记物；血液用于全身炎症标志物； 神经心理学测试；和调查（药物/健康史；口腔症状、卫生行为和 生活质量；健康的社会决定因素）。最后，我们将进行半结构化的深度访谈 探索与口腔健康和 AD 相关的社会决定因素。生成的数据将通知更大的 NIH 资助的研究，据我们所知，提供了最大和最全面的口腔特征 具有 AD 风险的不同种族个体样本中的微生物组。