Saliva based protein markers for predicting the risk of cognitive decline and dementia in older adults.

基于唾液的蛋白质标记物可预测老年人认知能力下降和痴呆的风险。

• 批准号: 10662974
• 负责人: Shalini Jain
• 金额: $ 18.74万
• 依托单位: UNIVERSITY OF SOUTH FLORIDA
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-06-01 至 2025-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10662974
• 关键词: Age; Age-associated memory impairment; Aging; Alzheimer' s Disease; Alzheimer' s disease pathology; Alzheimer' s disease patient; Alzheimer' s disease related dementia; Amyloid beta-Protein; Biological Markers; Blood; Brain; Brain imaging; Breast cancer metastasis; Cancer Detection; Cells; Cerebrospinal Fluid; Circulation; Clinical; Clinical Research; Clinical Trials; Cognition; Cognitive; Cohort Studies; Data; Databases; Dementia; Detection; Development; Diagnosis; Disease; Early Diagnosis; Elderly; Florida; Follow-Up Studies; Foundations; Frequencies; Funding; Goals; Head and neck structure; Healthcare Systems; Image; Impaired cognition; Individual; Inflammation; Inflammatory; Interleukin-1 beta; Interleukin-6; Knowledge; Link; Lymphatic; Lymphatic System; Magnetic Resonance Imaging; Measurement; Measures; Memory Loss; Monitor; Mucous Membrane; National Institute on Aging; Oral; Oral cavity; Oral health; Outcome Measure; Outcome Study; Participant; Patients; Peptides; Periodontitis; Plasma; Population; Positron-Emission Tomography; Prevalence; Prevention; Prognosis; Prognostic Marker; Proteins; Proteomics; Public Health; Publishing; Research; Resources; Retrospective Studies; Risk; Saliva; Salivary; Sampling; Societies; Symptoms; System; TNF gene; Testing; Training; United States Food and Drug Administration; biomarker panel; brain circulation; chemokine; clinical diagnosis; cohort; cost; cytokine; early detection biomarkers; early onset; family burden; follow-up; high risk; inflammatory marker; lymphatic circulation; macromolecule; microbial; microbial community; microbiome; mild cognitive impairment; minimally invasive; oral microbiome; predictive marker; prospective; protein biomarkers; proteomic signature; recruit; risk prediction; saliva proteome; systemic inflammatory response; tau Proteins; tau-1; Age; Age-associated memory impairment; Aging; Alzheimer' s Disease; Alzheimer' s disease pathology; Alzheimer' s disease patient; Alzheimer' s disease related dementia; Amyloid beta-Protein; Biological Markers; Blood; Brain; Brain imaging; Breast cancer metastasis; Cancer Detection; Cells; Cerebrospinal Fluid; Circulation; Clinical; Clinical Research; Clinical Trials; Cognition; Cognitive; Cohort Studies; Data; Databases; Dementia; Detection; Development; Diagnosis; Disease; Early Diagnosis; Elderly; Florida; Follow-Up Studies; Foundations; Frequencies; Funding; Goals; Head and neck structure; Healthcare Systems; Image; Impaired cognition; Individual; Inflammation; Inflammatory; Interleukin-1 beta; Interleukin-6; Knowledge; Link; Lymphatic; Lymphatic System; Magnetic Resonance Imaging; Measurement; Measures; Memory Loss; Monitor; Mucous Membrane; National Institute on Aging; Oral; Oral cavity; Oral health; Outcome Measure; Outcome Study; Participant; Patients; Peptides; Periodontitis; Plasma; Population; Positron-Emission Tomography; Prevalence; Prevention; Prognosis; Prognostic Marker; Proteins; Proteomics; Public Health; Publishing; Research; Resources; Retrospective Studies; Risk; Saliva; Salivary; Sampling; Societies; Symptoms; System; TNF gene; Testing; Training; United States Food and Drug Administration; biomarker panel; brain circulation; chemokine; clinical diagnosis; cohort; cost; cytokine; early detection biomarkers; early onset; family burden; follow-up; high risk; inflammatory marker; lymphatic circulation; macromolecule; microbial; microbial community; microbiome; mild cognitive impairment; minimally invasive; oral microbiome; predictive marker; prospective; protein biomarkers; proteomic signature; recruit; risk prediction; saliva proteome; systemic inflammatory response; tau Proteins; tau-1

Project Summary As our population ages, the prevalence of aging-related disorders such as cognitive decline, Alzheimer’s disease (AD), and its related dementia (ADRD) is increasing, with poor or no prognosis, prevention, and treatments. This, in turn, burdens families, society, and our healthcare system. Although, several recent advances have led to the development of prognostic markers of ADRD including advanced imaging like MRI, PET, and measurements of amyloid-β (Aβ) and tau proteins in cerebrospinal fluid (CSF) and blood; but their uses are impeded due to cost, invasiveness, and required frequency of measurements, with limitations in sensitivity and accuracy. Thus, developing new, non-invasive, sensitive, and easy to frequently measure with increased accuracy biomarkers for predicting the risk of early onset of cognitive decline and ADRD progression is direly needed. Saliva is an attractive reservoir of biomarkers that can noninvasively and inexpensively be collected with unlimited frequency. We hypothesize that saliva protein markers can differentiate mild cognitive impairment (MCI) and dementia from cognitively healthy individuals. We also posit that these saliva protein markers can predict the risk of MCI and dementia, and the inclusion of oral microbiome and systemic inflammatory markers will strengthen the discriminatory and predictive power. Our hypothesis is based on strong fundamental knowledge and preliminary data. The fact that the oral cavity’s mucosal and lymphatic systems are connected to the brain circulations and are in physical proximity, which allows the bidirectional exchange of molecules like proteins and peptides, between oral and brain systems. Abnormalities in the oral microbiome and systemic inflammation are linked to the risk of cognitive decline and ADRD, but these conclusions are drawn from small, cross-sectional, observational, and non-prospective risk prediction studies. Here, using our ongoing large clinical cohort- Microbiome in aging Gut and Brain (MiaGB) consortium study, we plan to globally analyze proteomics and oral microbiome in saliva along with markers of inflammation in plasma of 60 cognitively normal, 60 MCI, and 40 dementia participants in both cross-sectional and prospective follow-up studies to test our hypotheses. We plan two specific aims. In Aim 1 we will determine if unique proteomic signatures differentiate subjects with MCI and dementia from cognitively healthy controls and if the addition of microbiome and inflammatory markers boosts the distinction; and in Aim 2, we will determine if saliva-based protein markers predict the risk of MCI and dementia progression and whether the inclusion of microbiome and inflammation strengthens the prediction in older adults. Building on an already ongoing large study and supported by compelling preliminary data and complementary expert team and interlinked aims, our study is expected to establish proof of concept that saliva-based biomarkers will diagnose and predict the risk of cognitive decline and dementia progression, which is increasingly common, costly, and debilitating public health problems in older adults, while it is well aligned with the goals of PAR-22-094.

项目摘要 随着我们人口的年龄，与衰老有关的疾病的流行率，例如认知能力下降，阿尔茨海默氏症 疾病（AD）及其相关痴呆（ADRD）正在增加，预后较差或没有预后，并且 治疗。反过来，这是伯恩斯家庭，社会和我们的医疗保健系统。虽然，最近几个 进步导致了ADRD的预后标记的发展，包括MRI等高级成像， 脑脊液（CSF）和血液中淀粉样蛋白-β（Aβ）和tau蛋白的PET和TAU蛋白的测量；但是他们 由于成本，侵入性和所需的测量频率而阻碍用途，并有限制 灵敏度和准确性。这是开发新的，无创的，敏感且易于经常衡量的 提高准确性生物标志物，以预测认知能力下降和ADRD进展的早期发作风险 直接需要。唾液是一个有吸引力的生物标志物库，可以无创，廉价地 以无限频率收集。我们假设唾液蛋白标记可以区分轻度认知 认知健康个体的障碍（MCI）和痴呆症。我们还肯定了这些唾液蛋白 标记可以预测MCI和痴呆症的风险，以及口服微生物组和全身性的风险 炎症标记将增强歧视性和预测能力。我们的假设是基于 强大的基本知识和初步数据。口腔粘膜和淋巴的事实 系统连接到大脑循环，并处于物理接近度，这允许双向 口服和脑系统之间的蛋白质和胡椒粉等分子的交换。口腔异常 微生物组和全身性炎症与认知能力下降和ADRD的风险有关，但是这些 结论来自小型，横截面，观察性和非良性风险预测研究。 在这里，使用我们正在进行的大型临床队列微生物组中的衰老肠和大脑（Miagb）联盟研究， 我们计划在唾液中全球分析蛋白质组学和口服微生物组，以及炎症的标志 横截面和前瞻性的60个认知正常，60个MCI和40名痴呆参与者的血浆 后续研究以检验我们的假设。我们计划两个具体的目标。在AIM 1中，我们将确定是否唯一 蛋白质组学特征将受试者与MCI和痴呆症与认知健康对照区分开 添加微生物组和炎症标志物可以提高区别。在AIM 2中，我们将确定是否 基于唾液的蛋白质标志物可以预测MCI和痴呆进展的风险，以及是否包含在内 微生物组和感染强度使老年人预测。建立在已经持续的大型 学习和支持引人入胜的初步数据和互补的专家团队，以及相互联系的目标，我们 预计研究将建立概念证明，即基于唾液的生物标志物将诊断并预测风险 认知能力下降和痴呆进展，这越来越普遍，昂贵且使人衰弱 老年人的健康问题，而与PAR-22-094的目标保持一致。