Blood Biomarker Development and Validation in Chronic Traumatic Encephalopathy and Alzheimer's Disease and Alzheimer's Disease Related Dementias
慢性创伤性脑病、阿尔茨海默病和阿尔茨海默病相关痴呆的血液生物标记物开发和验证
基本信息
- 批准号:10662752
- 负责人:
- 金额:$ 194.07万
- 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 2025-05-31
- 项目状态:未结题
- 来源:
- 关键词:3-DimensionalAccelerationAddressAdoptionAdultAgeAgreementAlzheimer disease detectionAlzheimer&aposs DiseaseAlzheimer&aposs disease related dementiaAlzheimer&aposs disease riskAlzheimer’s disease biomarkerAmyloid beta-ProteinAutopsyBiological MarkersBloodBlood BanksBlood VesselsBostonBrainBrain ConcussionBrain Health RegistryCessation of lifeClinicClinicalCognitiveCollectionCraniocerebral TraumaDataDementiaDetectionDiagnosisDiagnosticDiagnostics ResearchDiseaseDoseEnrollmentEpidemiologyEpitopesExposure toFemaleFoundationsFrequenciesGeneticGlial Fibrillary Acidic ProteinGoalsGrantImpaired cognitionIndividualInfrastructureInternetKnowledgeLesionLifeLightLiteratureManufactured footballMass Spectrum AnalysisMeasuresMediatingMedicalMemoryMilitary PersonnelNational Institute of Neurological Disorders and StrokeNerve DegenerationNeuronsOutcomeParticipantPathologicPathologyPersonsPhosphorylation SitePlasmaPlayPopulation HeterogeneityPopulations at RiskPositron-Emission TomographyProbabilityProteinsRaceRegistriesResearchResourcesRiskRisk FactorsSamplingSeveritiesSiteSpecificitySurveysSynapsesSyndromeTestingTimeTissuesUnited States Department of Veterans AffairsUniversitiesVenous blood samplingViolenceWomanapolipoprotein E-4biomarker developmentbiomarker validationbrain basedcerebral atrophychronic traumatic encephalopathycognitive testingcontact sportsdementeddensitydiagnostic criteriadosageexecutive functionhead impactinfancymenmiddle agemilitary servicemilitary veteranneurobehavioralneurofilamentnon-dementedrecruitrepositoryresponsesexsubconcussionsurveillance studytau Proteinstau-1timeline
项目摘要
Each year, millions of people are exposed to repetitive head impacts (RHI) through contact sports, military
service, and physical violence. These impacts can confer risk for Alzheimer’s disease (AD) and related
dementias (ADRD) including chronic traumatic encephalopathy (CTE). The unique pathological lesion of CTE
includes phosphorylated tau (p-tau) in neurons around small blood vessels at the sulci. CTE still cannot be
diagnosed during life. Research diagnostic criteria for the clinical syndrome of CTE were developed by our team,
known as traumatic encephalopathy syndrome (TES). The TES criteria are non-specific and were developed
without biomarkers. To date, efforts on biomarkers for CTE have focused on those with low scalability and poor
accessibility (e.g., PET). It is now possible to detect AD/ADRD proteins in the blood, representing an accessible
alternative for disease detection. Research on plasma-brain associations in AD/ADRD is still in its infancy. The
literature on plasma biomarkers for CTE is even more nascent and plasma-to-autopsy studies are scarce, which
are vital for biomarker development and validation. This R01 will examine the ability of plasma biomarkers of p-
tau, Aβ, and neurodegeneration to detect CTE and its clinical syndrome (TES), and predict AD/ADRD pathology
in the brain. We will leverage the Brain Donation Registry (BDR) that is hosted online by the Concussion Legacy
Foundation (CLF). BDR individuals pledge their brain to research and are funneled to the Veteran Affairs-Boston
University (BU)-CLF brain bank—the largest repository of RHI tissue in the world (>1250 donors). We will ask
BDR individuals (n=1000; 800 RHI, 200 non-RHI; all 40+ years) to have a phlebotomy at a Quest lab for banking
at BioSEND. They will complete the UCSF-BU internet-based Brain Health Registry-Head Impact & Trauma
Surveillance Study for clinical characterization. The sample of 1000 will facilitate our long-term infrastructure
goal of large-scale blood banking on people at risk for CTE and AD/ADRD who agree to brain donation and are
clinically characterized. To test the R01 aims, plasma biomarker analyses will be done on 300 of the 1000: 200
RHI and 100 matched people without RHI. We will measure six p-tau epitopes (181+199+202+205+217+231),
Aβ40/42, total tau, glial fibrillary acidic protein, and neurofilament light. Of the 1000, we expect 100 brain
donations during the grant and the same analytes will be measured in blood and brain. 120 brain donors from
our BU ADRC bank have these plasma biomarkers available and will be used for autopsy-proven AD and non-
AD comparators. Aim 1 will compare plasma biomarkers between the 200 RHI and 100 non-RHI and test plasma
biomarker and clinical associations. Aim 2 will include plasma-to-autopsy studies using the 100 brain donations
enriched for CTE (people from the BDR) and the 120 BU ADRC donors with autopsy-proven AD and non-AD.
Aim 3 will test RHI and plasma biomarker associations. This R01 will lead to unprecedented data to develop and
validate plasma biomarkers for CTE. Large-scale blood banking from people across diverse exposures to RHI
who agreed to brain donation will create a unique resource to address unmet needs in AD/ADRD including CTE.
每年,数百万人通过接触性运动、军事和体育运动暴露于重复性头部撞击(RHI)。
服务和身体暴力这些影响可能会导致阿尔茨海默病(AD)和相关疾病的风险。
痴呆(ADRD),包括慢性创伤性脑病(CTE)。CTE的独特病理损害
包括脑沟处小血管周围神经元中的磷酸化tau(p-tau)。CTE仍然不能
在生活中诊断出来。CTE临床综合征的研究诊断标准由我们的团队开发,
创伤性脑病综合征(TES)工商业污水附加费标准并不具体,
没有生物标志物。到目前为止,CTE生物标志物的努力集中在那些具有低可扩展性和差的生物标志物上。
可访问性(例如,PET)。现在可以检测血液中的AD/ADRD蛋白,这代表了一种可获得的
疾病检测的替代方案。AD/ADRD的血浆-脑关联研究尚处于起步阶段。的
关于CTE的血浆生物标志物的文献甚至更是新生的,血浆到尸检的研究也很少,
对于生物标志物的开发和验证至关重要。本R 01将检查血浆中p-
tau蛋白、Aβ和神经退行性变检测CTE及其临床综合征(TES),并预测AD/ADRD病理
在大脑中。我们将利用脑震荡遗产在线托管的脑捐赠注册表(BDR)
基金会(CLF)。BDR个人承诺他们的大脑用于研究,并被输送到退伍军人事务-波士顿
大学(BU)-CLF脑库-世界上最大的RHI组织库(>1250名供体)。我们会要求
BDR个体(n=1000; 800例RHI,200例非RHI;均为40岁以上)在Quest实验室进行静脉切开术,用于银行业务
在BioSEND。他们将完成UCSF-BU基于互联网的脑健康登记-头部撞击和创伤
临床表征的监测研究。1000个样本将有助于我们的长期基础设施
大规模血库的目标是对有CTE和AD/ADRD风险的人,他们同意捐献大脑,
临床特征。为了测试R 01 aim,将对1000:200中的300例进行血浆生物标志物分析
RHI和100个匹配的没有RHI的人。我们将测量六个p-tau表位(181+199+202+205+217+231),
Aβ40/42、总tau、胶质细胞酸性蛋白和神经丝轻。在这1000人中,我们预计有100人是有头脑的
捐赠期间,将在血液和大脑中测量相同的分析物。120名大脑捐赠者,
我们的BU ADRC库有这些可用的血浆生物标志物,并将用于尸检证实的AD和非AD。
AD比较器。目的1将比较200例RHI和100例非RHI和试验血浆之间的血浆生物标志物
生物标志物和临床关联。目标2将包括使用100个大脑捐赠的血浆到尸检研究
富集CTE(来自BDR的人)和120名具有尸检证实的AD和非AD的BU ADRC供体。
目标3将测试RHI和血浆生物标志物的关联。R 01将带来前所未有的数据开发,
验证CTE的血浆生物标志物。来自不同RHI暴露人群的大规模血库
同意捐赠大脑的人将创建一个独特的资源,以解决AD/ADRD(包括CTE)中未满足的需求。
项目成果
期刊论文数量(1)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Optimal blood tau species for the detection of Alzheimer's disease neuropathology: an immunoprecipitation mass spectrometry and autopsy study.
- DOI:10.1007/s00401-023-02660-3
- 发表时间:2023-12-30
- 期刊:
- 影响因子:12.7
- 作者:
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Michael Alosco其他文献
Michael Alosco的其他文献
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{{ truncateString('Michael Alosco', 18)}}的其他基金
Validation of Lens Beta-Amyloid as a Novel Biomarker for Early Detection of Alzheimer's Disease at the Boston University Alzheimer's Disease Research
波士顿大学阿尔茨海默病研究中心验证晶状体 β-淀粉样蛋白作为早期检测阿尔茨海默病的新型生物标志物
- 批准号:
10591150 - 财政年份:2023
- 资助金额:
$ 194.07万 - 项目类别:
Late Pathologies of Exposure to Repetitive Head Impacts from Contact Sports: White Matter and Vascular Contributions to Cognitive Impairment, Dementia, and Neuropsychiatric Symptoms
接触性运动造成的重复性头部撞击的晚期病理学:白质和血管对认知障碍、痴呆和神经精神症状的影响
- 批准号:
10276270 - 财政年份:2021
- 资助金额:
$ 194.07万 - 项目类别:
In Vivo Detection of Chronic Traumatic Encephalopathy with 18F-MK-6240 Tau PET
使用 18F-MK-6240 Tau PET 体内检测慢性创伤性脑病
- 批准号:
10323058 - 财政年份:2021
- 资助金额:
$ 194.07万 - 项目类别:
Risk for Later-Life Cognitive Impairment, Neurobehavioral Dysregulation, and Dementia in Former Soccer and American Football Players: The Head Impact and Trauma Surveillance Study (HITSS)
前足球和美式橄榄球运动员晚年认知障碍、神经行为失调和痴呆的风险:头部撞击和创伤监测研究 (HITSS)
- 批准号:
10563183 - 财政年份:2021
- 资助金额:
$ 194.07万 - 项目类别:
Contributions of Exposure to Traumatic Brain Injury and Repetitive Head Impacts to Alzheimer's Disease and Related Dementias and Chronic Traumatic Encephalopathy
暴露于创伤性脑损伤和重复性头部撞击对阿尔茨海默病和相关痴呆以及慢性创伤性脑病的影响
- 批准号:
10460265 - 财政年份:2019
- 资助金额:
$ 194.07万 - 项目类别:
Contributions of Exposure to Traumatic Brain Injury and Repetitive Head Impacts to Alzheimer's Disease and Related Dementias and Chronic Traumatic Encephalopathy
暴露于创伤性脑损伤和重复性头部撞击对阿尔茨海默病和相关痴呆以及慢性创伤性脑病的影响
- 批准号:
10227042 - 财政年份:2019
- 资助金额:
$ 194.07万 - 项目类别:
Contributions of Exposure to Traumatic Brain Injury and Repetitive Head Impacts to Alzheimer's Disease and Related Dementias and Chronic Traumatic Encephalopathy
暴露于创伤性脑损伤和重复性头部撞击对阿尔茨海默病和相关痴呆以及慢性创伤性脑病的影响
- 批准号:
10021467 - 财政年份:2019
- 资助金额:
$ 194.07万 - 项目类别:
Repetitive Head Impact Exposure and Later-Life White Matter Signal Abnormalities: An Investigation in Former NFL Players, Subjects with Alzheimer's Disease, and Cognitively Normal Controls
重复头部撞击暴露和晚年白质信号异常:对前 NFL 球员、阿尔茨海默氏病受试者和认知正常对照的调查
- 批准号:
10406252 - 财政年份:2018
- 资助金额:
$ 194.07万 - 项目类别:
Repetitive Head Impact Exposure and Later-Life White Matter Signal Abnormalities: An Investigation in Former NFL Players, Subjects with Alzheimer's Disease, and Cognitively Normal Controls
重复头部撞击暴露和晚年白质信号异常:对前 NFL 球员、阿尔茨海默氏病受试者和认知正常对照的调查
- 批准号:
10176610 - 财政年份:2018
- 资助金额:
$ 194.07万 - 项目类别:
Repetitive Head Impact Exposure and Later-Life White Matter Signal Abnormalities: An Investigation in Former NFL Players, Subjects with Alzheimer's Disease, and Cognitively Normal Controls
重复头部撞击暴露和晚年白质信号异常:对前 NFL 球员、阿尔茨海默氏病受试者和认知正常对照的调查
- 批准号:
9921499 - 财政年份:2018
- 资助金额:
$ 194.07万 - 项目类别:
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