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

摘要 阿尔茨海默病(AD)影响着650万美国人，给我们的社会带来了巨大的负担 从经济和人类痛苦的角度来看，阿尔茨海默病的病因尚不完全清楚。AD的危险因素 数量众多，包括人口、遗传、生活方式、医疗、环境、精神疾病和传染性 各种因素。已知的与阿尔茨海默病相关的感染因素包括牙周病(期间)。期间 是一种牙龈组织的多菌感染，也是口腔最常见的疾病之一。 人们对周期和AD之间的联系越来越感兴趣，但其潜在的机制 这种联系是未知的，大多数研究都将调查集中在有限的几个时期- 相关生物，如牙龈卟啉单胞菌、连翘坦纳氏菌和齿密螺旋体。 目前，该领域的一个主要和根本的障碍是缺乏跨王国(细菌、病毒、真菌)， 口腔微生物群的综合特征，因为它与AD风险有关。总的目的 拟议项目的一部分是调查口腔微生物组在高危人群中的临床相关性。 对于AD。150名中年人将参加这项纵向队列研究。主要目标是 口腔细菌、病毒和真菌在认知正常人群中的分类和功能特征 面临阿尔茨海默病的风险，在两年的时间里，调查与时期相关的微生物群之间的关系 口腔健康的特征、炎症、社会决定因素和AD-CSF生物标记物(Aβ42、TOTAL-TAU和 磷酸-Tau)。我们将利用现有的NIH资助的、特征良好的队列，其中包括种族多元化 AD高危个体(通过家族病史或APOE4等位基因)。学员将完成3次考察访问 每年一次。AD和炎症标志物的脑脊液将在基线和Yr2采集。每年一次 评估和标本采集将包括：临床口腔检查； 微生物组评估；唾液检测炎症标志物；血液检测全身炎症标志物； 神经心理测试；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采访， 探讨口腔健康与阿尔茨海默病的社会决定因素。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 不同种族的阿尔茨海默病高危人群样本中的微生物群。

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.