In vivo staging of preclinical Alzheimer's disease progression

临床前阿尔茨海默病进展的体内分期

基本信息

批准号：
9759751
负责人：
Robert Nathan Spreng
金额：
$ 5.23万
依托单位：
MCGILL UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-08-15 至 2021-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9759751
关键词：
Address Adult Affect Alzheimer disease prevention Alzheimer&apos s Disease Alzheimer’s disease biomarker Amyloid beta-Protein Anatomy Area Attentional deficit Axon Biological Biological Markers Biomedical Engineering Brain Brain region Cells Cerebrospinal Fluid Clinic Clinical Cognition Data Data Collection Data Set Databases Development Diagnosis Diagnostic Disease Disease Progression Early Diagnosis Economics Effectiveness Exhibits Funding Future Gene Expression Genetic Transcription Goals Human Impaired cognition Individual Intervention Label Laboratories Length Magnetic Resonance Imaging Maps Measures Methods National Institute on Aging Neurobehavioral Manifestations Neurons Pathologic Pathology Pattern Phase Prognostic Marker Protocols documentation Quality of life RNA Research Staging Structural Genes Structure System Testing Time Work basal forebrain basal forebrain cholinergic neurons base bioimaging cell type cholinergic cholinergic neuron data integration diagnostic biomarker effective therapy functional genomics genomic data gray matter healthy aging in vivo meter mild cognitive impairment multimodal data neuroimaging novel pre-clinical selective attention social therapeutic development

项目摘要

PROJECT SUMMARY/ABSTRACT The social, economic and personal burden of Alzheimer's disease (AD) is rapidly climbing in the U.S. with diagnoses expected to more than double over the next three decades. At the same time, our understanding of the brain changes associated with AD is increasing exponentially, and promising interventions to slow or halt the progress of the disease are beginning to move from the laboratory into the clinic. In this context, the development of approaches to aid early detection of the transition from healthy aging to mild cognitive impairment (MCI) and AD is becoming critically important. The Alzheimer's Disease Neuroimaging Initiative (ADNI), funded by the National Institutes of Aging and Bioimaging and Bioengineering, was launched in 2005 to provide a large database data to develop diagnostic and prognostic biomarkers of AD. While the overarching goal of this longitudinal data collection initiative is to provide information and methods leading to effective treatment and prevention of AD, the significant promise of in vivo neuroimaging in this area has yet to be fully realized. However, we can now reliably detect AD in humans based on biological markers, sometimes decades before cognitive symptoms emerge based upon cerebrospinal fluid (CSF) concentrations of the amyloid beta peptide 1-42 (Aβ) The advent of the CSF Aβ biomarker opens a window for studying the pathological progression of AD at preclinical stages of disease in humans. We will capitalize on the rich array of multi-modal data available through the ADNI to integrate structural MRI and gene expression data, in combination with the CSF Aβ biomarker, to (i) identify cell-type specific degeneration of the cholinergic basal forebrain neurons across preclinical and mild cognitive impairment stages of AD, and (ii) map the subcortical-to-cortical spread of cholinergic degeneration by examining the covariance of structural degeneration between the basal forebrain and cortex.

项目摘要/摘要阿尔茨海默氏病（AD）的社会，经济和个人燃烧正在美国迅速攀升在未来三十年中，诊断预计将增加两倍以上。同时，我们对与AD相关的大脑变化呈指数增加，并承诺干预措施缓慢或停止疾病的进展开始从实验室转移到诊所。在这种情况下，开发方法以帮助早期发现从健康衰老到轻度认知的过渡障碍（MCI）和AD变得非常重要。阿尔茨海默氏病神经影像倡议（ADNI）由美国国家老化与生物成像和生物工程资助，于2005年启动提供大型数据库数据以开发AD的诊断和预后生物标志物。而总体这项纵向数据收集计划的目标是提供信息和方法，导致有效治疗和预防AD，该领域的体内神经影像学的重大希望尚未完全实现。但是，我们现在可以根据生物学标记可靠地在人类中可靠地检测AD，有时数十年淀粉样蛋白β的脑脊液（CSF）浓度在认知症状之前出现之前肽1-42（Aβ）CSFAβ生物标志物的冒险为研究病理的窗口打开了一个窗口在人类疾病的临床前阶段AD的进展。我们将利用丰富的多模式通过ADNI获得的数据以整合结构MRI和基因表达数据，并结合 CSFAβ生物标志物，要（i）识别胆碱能基本前脑神经元的细胞类型特异性变性跨AD的临床前和轻度认知障碍阶段，以及（ii）绘制皮层下皮层的扩散通过检查基本前脑之间结构变性的协方差，胆碱能变性和皮质。

项目成果

期刊论文数量（4）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Longitudinal Basal Forebrain Degeneration Interacts with TREM2/C3 Biomarkers of Inflammation in Presymptomatic Alzheimer's Disease.

纵向基底前脑变性与阿尔茨海默病症状前炎症的 TREM2/C3 生物标志物相互作用。

DOI：
10.1523/jneurosci.1184-19.2019
发表时间：
2020
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
0
作者：
Schmitz,TaylorW;Soreq,Hermona;Poirier,Judes;Spreng,RNathan
通讯作者：
Spreng,RNathan

Intrinsic neurocognitive network connectivity differences between normal aging and mild cognitive impairment are associated with cognitive status and age.

DOI：
10.1016/j.neurobiolaging.2018.10.001
发表时间：
2019-01
期刊：
Neurobiology of aging
影响因子：
4.2
作者：
Sullivan MD;Anderson JAE;Turner GR;Spreng RN;Alzheimer's Disease Neuroimaging Initiative
通讯作者：
Alzheimer's Disease Neuroimaging Initiative