CSF, MRI, and PET biomarkers of neuroinflammation in Alzheimer's disease
阿尔茨海默病神经炎症的 CSF、MRI 和 PET 生物标志物
基本信息
- 批准号:9976071
- 负责人:
- 金额:$ 9.99万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2016
- 资助国家:美国
- 起止时间:2016-08-15 至 2021-05-31
- 项目状态:已结题
- 来源:
- 关键词:AcuteAlgorithmsAlzheimer&aposs DiseaseAlzheimer&aposs disease diagnosisAlzheimer&aposs disease pathologyAnti-Inflammatory AgentsAutopsyBiochemicalBiological AssayBiological MarkersBlood - brain barrier anatomyBlood VesselsBrainBrain imagingCellsCerebrospinal FluidCessation of lifeChronicClinical TrialsCognitiveCognitive deficitsComplementComplement ActivationComplement SuppressionDataDementiaDevelopmentEncephalitisEventFDA approvedFractalkineFutureHelper-Inducer T-LymphocyteHumanImageImaging ligandsImmune systemImmunomodulatorsImmunophenotypingImpaired cognitionIndividualInflammationInflammatoryInterleukin-10Interleukin-7IronLabelLigandsLinkLiquid substanceMRI ScansMachine LearningMagnetic Resonance ImagingMeasurementMeasuresMediatingMethodsModalityModernizationNeurodegenerative DisordersOutcomePathogenesisPathway AnalysisPathway interactionsPatientsPatternPattern RecognitionPeptidesPeripheralPhagocytesPhenotypePopulationPositron-Emission TomographyProcessProteinsRegulationRoleSpecificitySymptomsSystemT-Cell ActivationT-LymphocyteTestingTherapeuticTracerbioinformatics pipelinebiomarker panelbrain dysfunctioncell typechemokinecohortcytokinedemographicsgenetic variantimaging biomarkerinflammatory markerinsightiron oxidemacrophagemigrationmild cognitive impairmentmolecular imagingneuroinflammationneuropathologyneuroprotectionnovel
项目摘要
ABSTRACT
Alzheimer’s disease (AD) is the most common form of neurodegenerative disorder. Inflammatory
changes in the brain are thought to represent key processes in the onset and progression of AD, but
it remains unclear whether neuroinflammation confers neuroprotection, accelerated degeneration, or
possibly both. Such an understanding in living humans is critical if we are to begin clinical trials using
the array of FDA-approved immunomodulatory drugs in the future. We propose that complement-
mediated neuroinflammation is protective in the early AD stages, while suppression of complement
activities is accompanied by the development of greater cognitive deficits and faster cognitive decline.
Our preliminary data from multiple cohorts support this hypothesis by showing 1) reduced levels of
cerebrospinal fluid (CSF) complement-related markers occur in the dementia stage but not mild
cognitive impairment (MCI) stage of AD; 2) reduced CSF complement-related markers and elevated
CSF interleukin-10 (IL-10) levels are associated with faster decline in AD; and 3) CSF inflammatory
protein alterations reveal networks of cellular and protein regulations. In the In the current
application, we will build on the association between complement related proteins and rates of
cognitive decline in AD to identify associated changes in soluble CSF cytokines and chemokines,
differential inflammatory cell type regulation, and imaging correlates of neuroinflammation. This
application takes advantage of our group’s strengths in performing CSF cytokine measurements, CSF
immunophenotyping, molecular imaging of neuroinflammation through positron emission tomography
(PET) and iron-enhanced MRI, and network analysis through a novel biochemical-bioinformatics
pipeline. We will directly identify individual and networks of soluble CSF cytokines that accompany
the transition from the MCI to the dementia stage of AD, correlate the complement and other altered
pathways with microglial activation through two modern PET tracers (11C-PBR28 and 18F-FEPPA),
and measure changes in individual T helper cell (type 1, 2, 17) and non-T cell populations. This
application represents the first attempt to correlate, at the individual level and at the group level, CSF
and imaging measures of neuroinflammation. If successful, this application will advance the
understanding of neuroinflammation in AD through parallel approaches, form the basis of a new
biomarker panel (and algorithm) to diagnose AD through a combination of degenerative and
inflammatory markers, and accelerate the target identification of future therapeutics aimed at
modulating the immune system in AD.
摘要
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 }}
William Tzu-lung Hu其他文献
William Tzu-lung Hu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('William Tzu-lung Hu', 18)}}的其他基金
Resource Center for Alzheimer's and Dementia Research in Asian and Pacific Americans
亚太裔美国人阿尔茨海默病和痴呆症研究资源中心
- 批准号:
10730059 - 财政年份:2023
- 资助金额:
$ 9.99万 - 项目类别:
Neurological and digital correlates of cognition in Older Mandarin-speaking Adults
普通话老年人认知的神经和数字相关性
- 批准号:
10608780 - 财政年份:2022
- 资助金额:
$ 9.99万 - 项目类别:
Role of estradiol and related hormones on inflammation, sleep, and risks for Alzheimer's disease
雌二醇和相关激素对炎症、睡眠和阿尔茨海默病风险的作用
- 批准号:
10663189 - 财政年份:2019
- 资助金额:
$ 9.99万 - 项目类别:
Role of estradiol and related hormones on inflammation, sleep, and risks for Alzheimer's disease
雌二醇和相关激素对炎症、睡眠和阿尔茨海默病风险的作用
- 批准号:
10017867 - 财政年份:2019
- 资助金额:
$ 9.99万 - 项目类别:
Role of estradiol and related hormones on inflammation, sleep, and risks for Alzheimer's disease
雌二醇和相关激素对炎症、睡眠和阿尔茨海默病风险的作用
- 批准号:
10458043 - 财政年份:2019
- 资助金额:
$ 9.99万 - 项目类别:
Role of estradiol and related hormones on inflammation, sleep, and risks for Alzheimer's disease
雌二醇和相关激素对炎症、睡眠和阿尔茨海默病风险的作用
- 批准号:
10240604 - 财政年份:2019
- 资助金额:
$ 9.99万 - 项目类别:
Role of estradiol and related hormones on inflammation, sleep, and risks for Alzheimer's disease
雌二醇和相关激素对炎症、睡眠和阿尔茨海默病风险的作用
- 批准号:
9891680 - 财政年份:2019
- 资助金额:
$ 9.99万 - 项目类别:
Transfer RF1 AG054991 Beyond Haploinsuffiency- Gain of Function in Prograulin Mutations
转移 RF1 AG054991 超越单倍体不足 - Prograulin 突变的功能获得
- 批准号:
10399043 - 财政年份:2019
- 资助金额:
$ 9.99万 - 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:
$ 9.99万 - 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:
$ 9.99万 - 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:
$ 9.99万 - 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:
$ 9.99万 - 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:
$ 9.99万 - 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:
$ 9.99万 - 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:
$ 9.99万 - 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:
$ 9.99万 - 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:
$ 9.99万 - 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:
$ 9.99万 - 项目类别:
Continuing Grant