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。
基本信息
- 批准号:10662974
- 负责人:
- 金额:$ 18.74万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 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:
- 关键词:AgeAge-associated memory impairmentAgingAlzheimer&aposs DiseaseAlzheimer&aposs disease pathologyAlzheimer&aposs disease patientAlzheimer&aposs disease related dementiaAmyloid beta-ProteinBiological MarkersBloodBrainBrain imagingBreast cancer metastasisCancer DetectionCellsCerebrospinal FluidCirculationClinicalClinical ResearchClinical TrialsCognitionCognitiveCohort StudiesDataDatabasesDementiaDetectionDevelopmentDiagnosisDiseaseEarly DiagnosisElderlyFloridaFollow-Up StudiesFoundationsFrequenciesFundingGoalsHead and neck structureHealthcare SystemsImageImpaired cognitionIndividualInflammationInflammatoryInterleukin-1 betaInterleukin-6KnowledgeLinkLymphaticLymphatic SystemMagnetic Resonance ImagingMeasurementMeasuresMemory LossMonitorMucous MembraneNational Institute on AgingOralOral cavityOral healthOutcome MeasureOutcome StudyParticipantPatientsPeptidesPeriodontitisPlasmaPopulationPositron-Emission TomographyPrevalencePreventionPrognosisPrognostic MarkerProteinsProteomicsPublic HealthPublishingResearchResourcesRetrospective StudiesRiskSalivaSalivarySamplingSocietiesSymptomsSystemTNF geneTestingTrainingUnited States Food and Drug Administrationbiomarker panelbrain circulationchemokineclinical diagnosiscohortcostcytokineearly detection biomarkersearly onsetfamily burdenfollow-uphigh riskinflammatory markerlymphatic circulationmacromoleculemicrobialmicrobial communitymicrobiomemild cognitive impairmentminimally invasiveoral microbiomepredictive markerprospectiveprotein biomarkersproteomic signaturerecruitrisk predictionsaliva proteomesystemic inflammatory responsetau Proteinstau-1
项目摘要
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
随着人口老龄化,与衰老有关的疾病,如认知能力下降,阿尔茨海默氏症,
疾病(AD)及其相关痴呆(ADRD)的发病率正在增加,预后差或无预后,预防,
治疗。这反过来又给家庭、社会和我们的医疗保健系统带来负担。虽然,最近几次
进展导致ADRD的预后标记物的发展,包括先进的成像如MRI,
PET,以及脑脊液(CSF)和血液中淀粉样蛋白-β(Aβ)和tau蛋白的测量;但其
由于成本、侵入性和所需的测量频率,
灵敏度和准确度。因此,开发新的、非侵入性的、敏感的和易于频繁测量的
预测认知功能减退和ADRD进展早发风险的生物标志物准确性提高
非常需要。唾液是生物标志物的一个有吸引力的储库,可以非侵入性和廉价地
以无限的频率收集。我们假设唾液蛋白标记物可以区分轻度认知障碍,
认知功能障碍(MCI)和痴呆的认知健康个体。我们还发现这些唾液蛋白
标记物可以预测MCI和痴呆的风险,包括口腔微生物组和全身性
炎性标志物将加强区分和预测能力。我们的假设是基于
扎实的基础知识和初步数据。口腔的粘膜和淋巴
系统连接到大脑循环,并在物理上接近,这允许双向
蛋白质和肽等分子在口腔和大脑系统之间的交换。在口头上的ababbilateral
微生物组和全身性炎症与认知能力下降和ADRD的风险有关,但这些
结论来自小型、横断面、观察性和非前瞻性风险预测研究。
在这里,使用我们正在进行的大型临床队列-老化肠道和大脑(MiaGB)联盟研究中的微生物组,
我们计划在全球范围内分析唾液中的蛋白质组学和口腔微生物组,
60名认知正常者、60名MCI和40名痴呆参与者的血浆,
后续研究来验证我们的假设。我们有两个具体目标。在目标1中,我们将确定是否唯一
蛋白质组特征将MCI和痴呆受试者与认知健康对照区分开来,
添加微生物组和炎症标志物可以增强区分;在目标2中,我们将确定
基于唾液的蛋白质标记物可预测MCI和痴呆进展的风险,
微生物组和炎症加强了老年人的预测。建立在一个已经在进行的大型
在令人信服的初步数据、互补的专家团队和相互关联的目标的支持下,
一项研究预计将建立基于唾液的生物标志物将诊断和预测风险的概念证据
认知能力下降和痴呆症进展,这是越来越常见,昂贵,并削弱公众
老年人的健康问题,同时它与PAR-22-094的目标保持一致。
项目成果
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