Longitudinal validation of retinal biomarkers against cerebral imaging in preclinical Alzheimer's disease

针对临床前阿尔茨海默病脑成像的视网膜生物标志物的纵向验证

基本信息

  • 批准号:
    10524682
  • 负责人:
  • 金额:
    $ 256.64万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2022
  • 资助国家:
    美国
  • 起止时间:
    2022-09-15 至 2027-05-31
  • 项目状态:
    未结题

项目摘要

Project Summary/Abstract Alzheimer’s disease (AD) is a gradually progressive neurodegenerative disorder that results in total cognitive and functional loss. To date, disease-modifying therapeutics and secondary prevention efforts have proven ineffective in combating this public health burden, which impacts over 5.8 million individuals, and is the 6th leading cause of death in the United States. The proposed study addresses the critical need for minimally invasive, cost-efficient, scalable, and accessible AD risk screening biomarkers capable of detecting AD in the earliest pathologic stages (preclinical AD) before clinical symptoms are evident. We target biomarkers in the human retina, a part of the central nervous system (CNS), as they can be visualized non-invasively using standard ophthalmologic techniques and show promise for early AD risk detection and disease monitoring. The Atlas of Retinal Imaging in Alzheimer’s Study (ARIAS) is a longitudinal, observational cohort study to identify sensitive and specific retinal biomarkers of preclinical AD and define their context of use. The objective of the proposed project is to leverage the existing ARIAS infrastructure, adding reference standard brain imaging biomarkers (3T MRI, Ab PET) and novel plasma biomarkers (ptau231, ptau181) to test the central hypothesis that retinal biomarker alterations will predict cerebral biomarker changes and mirror longitudinal cerebral biomarker changes in preclinical AD. Four specific aims will be pursued: (1) identify retinal biomarker differences between preclinical AD participants and cognitively unimpaired (CU) older adults; (2) validate candidate retinal biomarkers cross-sectionally against cerebral biomarkers using Ab PET as a measure of cerebral amyloidosis and MRI as a measure of neurodegeneration; (3) determine the longitudinal relationship between retinal and brain imaging biomarkers, and the ability of baseline retinal biomarkers to predict cognitive and/or brain imaging biomarker changes over 3-year follow-up; and (4) (exploratory) assess the combined sensitivity and specificity of candidate retinal biomarkers with emergent plasma biomarkers in AD risk prediction. Work will be carried out at one existing ARIAS site and two high performing AD research sites. CU participants will complete 5 study visits: screening, baseline, year (Y) 1, Y2, and Y3 follow-up. Brain imaging (MRI and Ab PET) and plasma analysis will occur at baseline and Y3 follow-up. Retinal imaging and cognitive evaluation will occur at baseline and Y1, Y2, and Y3 follow-up. Brain imaging, retinal imaging, cognitive evaluation, and plasma analysis will be supported by four respective cores. Validating retinal biomarkers in preclinical AD is expected to shift focus in AD retinal biomarker development towards systemic, quantitative characterization of retinal risk biomarkers scalable for population-based AD risk screening. Combining plasma biomarkers with sensitive and specific retinal biomarkers could transform AD risk assessment, allowing identification of AD-related changes decades before clinical onset, which may offer the best chance of therapeutic success. Clinical applications include population-based screening for ideal candidates for emerging secondary prevention therapeutics.
项目总结/摘要 阿尔茨海默病(Alzheimer's disease,AD)是一种渐进性神经退行性疾病, 功能丧失。迄今为止,疾病修饰疗法和二级预防工作已经证明, 在应对这一影响580多万人的公共卫生负担方面效果不佳, 美国的主要死因。拟议的研究解决了最低限度的迫切需要, 具有侵入性、成本效益高、可扩展和可获得的AD风险筛查生物标志物,能够在 在临床症状明显之前的最早病理阶段(临床前AD)。我们的目标是生物标志物, 人类视网膜,中枢神经系统(CNS)的一部分,因为它们可以使用非侵入性可视化 标准眼科技术并显示出早期AD风险检测和疾病监测的希望。的 阿尔茨海默病视网膜成像研究图谱(阿里亚斯)是一项纵向观察性队列研究, 临床前AD的敏感性和特异性视网膜生物标志物,并定义其使用背景。的目的 拟议的项目是利用现有的阿里亚斯基础设施,增加参考标准脑成像 生物标志物(3 T MRI、Ab PET)和新型血浆生物标志物(ptau 231、ptau 181),以检验中心假设 视网膜生物标志物的改变将预测大脑生物标志物的变化, 临床前AD的生物标志物变化。本研究的目的有四:(1)确定视网膜生物标志物的差异 临床前AD参与者和认知未受损(CU)老年人之间的差异;(2)验证候选视网膜病变 使用Ab PET作为脑淀粉样变性的量度,将生物标志物与脑生物标志物进行横断面对比 和MRI作为神经退行性变的量度;(3)确定视网膜和 脑成像生物标志物,以及基线视网膜生物标志物预测认知和/或脑成像的能力 3年随访期间生物标志物的变化;(4)(探索性)评估联合敏感性和特异性 候选视网膜生物标志物与紧急血浆生物标志物在AD风险预测中的比较。将开展工作, 一个现有的阿里亚斯站点和两个高性能AD研究站点。参加者将完成5项研究 访视:筛选、基线、第1年(Y)、第2年和第3年随访。脑成像(MRI和Ab PET)和血浆 分析将在基线和第3年随访时进行。基线时进行视网膜成像和认知评估 以及Y1、Y2和Y3随访。脑成像、视网膜成像、认知评估和血浆分析将在 由四个各自的核心支持。在临床前AD中验证视网膜生物标志物有望将焦点转移到 AD视网膜生物标志物的开发,以实现视网膜风险生物标志物的系统性定量表征 可扩展用于基于人群的AD风险筛查。将血浆生物标志物与敏感性和特异性 视网膜生物标志物可以改变AD风险评估,允许数十年来识别AD相关变化 在临床发作之前,这可能提供治疗成功的最佳机会。临床应用包括 以人群为基础筛选新兴二级预防疗法的理想候选人。

项目成果

期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ monograph.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ sciAawards.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ conferencePapers.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ patent.updateTime }}

Jessica Alber其他文献

Jessica Alber的其他文献

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

{{ truncateString('Jessica Alber', 18)}}的其他基金

Longitudinal validation of retinal biomarkers against cerebral imaging in preclinical Alzheimer's disease
针对临床前阿尔茨海默病脑成像的视网膜生物标志物的纵向验证
  • 批准号:
    10704641
  • 财政年份:
    2022
  • 资助金额:
    $ 256.64万
  • 项目类别:
Development of Retinal Biomarkers in Autosomal Dominant Alzheimer's Disease: A pilot study
常染色体显性阿尔茨海默病视网膜生物标志物的开发:一项试点研究
  • 批准号:
    10300246
  • 财政年份:
    2021
  • 资助金额:
    $ 256.64万
  • 项目类别:

相似海外基金

DMS-EPSRC: Asymptotic Analysis of Online Training Algorithms in Machine Learning: Recurrent, Graphical, and Deep Neural Networks
DMS-EPSRC:机器学习中在线训练算法的渐近分析:循环、图形和深度神经网络
  • 批准号:
    EP/Y029089/1
  • 财政年份:
    2024
  • 资助金额:
    $ 256.64万
  • 项目类别:
    Research Grant
CAREER: Blessing of Nonconvexity in Machine Learning - Landscape Analysis and Efficient Algorithms
职业:机器学习中非凸性的祝福 - 景观分析和高效算法
  • 批准号:
    2337776
  • 财政年份:
    2024
  • 资助金额:
    $ 256.64万
  • 项目类别:
    Continuing Grant
CAREER: From Dynamic Algorithms to Fast Optimization and Back
职业:从动态算法到快速优化并返回
  • 批准号:
    2338816
  • 财政年份:
    2024
  • 资助金额:
    $ 256.64万
  • 项目类别:
    Continuing Grant
CAREER: Structured Minimax Optimization: Theory, Algorithms, and Applications in Robust Learning
职业:结构化极小极大优化:稳健学习中的理论、算法和应用
  • 批准号:
    2338846
  • 财政年份:
    2024
  • 资助金额:
    $ 256.64万
  • 项目类别:
    Continuing Grant
CRII: SaTC: Reliable Hardware Architectures Against Side-Channel Attacks for Post-Quantum Cryptographic Algorithms
CRII:SaTC:针对后量子密码算法的侧通道攻击的可靠硬件架构
  • 批准号:
    2348261
  • 财政年份:
    2024
  • 资助金额:
    $ 256.64万
  • 项目类别:
    Standard Grant
CRII: AF: The Impact of Knowledge on the Performance of Distributed Algorithms
CRII:AF:知识对分布式算法性能的影响
  • 批准号:
    2348346
  • 财政年份:
    2024
  • 资助金额:
    $ 256.64万
  • 项目类别:
    Standard Grant
CRII: CSR: From Bloom Filters to Noise Reduction Streaming Algorithms
CRII:CSR:从布隆过滤器到降噪流算法
  • 批准号:
    2348457
  • 财政年份:
    2024
  • 资助金额:
    $ 256.64万
  • 项目类别:
    Standard Grant
EAGER: Search-Accelerated Markov Chain Monte Carlo Algorithms for Bayesian Neural Networks and Trillion-Dimensional Problems
EAGER:贝叶斯神经网络和万亿维问题的搜索加速马尔可夫链蒙特卡罗算法
  • 批准号:
    2404989
  • 财政年份:
    2024
  • 资助金额:
    $ 256.64万
  • 项目类别:
    Standard Grant
CAREER: Efficient Algorithms for Modern Computer Architecture
职业:现代计算机架构的高效算法
  • 批准号:
    2339310
  • 财政年份:
    2024
  • 资助金额:
    $ 256.64万
  • 项目类别:
    Continuing Grant
CAREER: Improving Real-world Performance of AI Biosignal Algorithms
职业:提高人工智能生物信号算法的实际性能
  • 批准号:
    2339669
  • 财政年份:
    2024
  • 资助金额:
    $ 256.64万
  • 项目类别:
    Continuing Grant
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了