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.

项目概要/摘要在美国，阿尔茨海默病 (AD) 的社会、经济和个人负担正在迅速攀升与此同时，我们对疾病的了解预计将在未来三十年增加一倍以上。与 AD 相关的大脑变化正在呈指数级增长，并且有希望采取干预措施来减缓或停止在此背景下，疾病的进展开始从实验室走向临床。开发方法来帮助及早发现从健康老龄化到轻度认知的转变阿尔茨海默氏病神经影像计划变得至关重要。 (ADNI)，由美国国立老龄化、生物成像和生物工程研究所资助，于 2005 年启动提供大型数据库数据来开发 AD 的诊断和预后生物标志物。这一纵向数据收集举措的目标是提供信息和方法，以实现有效的 AD 的治疗和预防，体内神经影像学在这一领域的重大前景尚未得到充分体现然而，我们现在可以根据生物标记可靠地检测人类的 AD，有时需要几十年的时间。根据脑脊液 (CSF) β 淀粉样蛋白浓度，在出现认知症状之前肽 1-42 (Aβ) CSF Aβ 生物标志物的出现为研究病理学打开了窗口我们将利用丰富的多模式研究 AD 在人类疾病临床前阶段的进展。 ADNI 提供的数据可整合结构 MRI 和基因表达数据，并结合 CSF Aβ 生物标志物，用于 (i) 识别胆碱能基底前脑神经元的细胞类型特异性变性跨越 AD 的临床前和轻度认知障碍阶段，以及 (ii) 绘制皮质下到皮质的传播图通过检查基底前脑之间结构变性的协方差来确定胆碱能变性和皮质。

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