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

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,数以百万计的人暴露在重复性的头部撞击(RHI)通过身体接触运动,军事

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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