Large artery stiffness and cerebrovascular dysfunction: Implications for cognitive impairment and neuropathology
大动脉僵硬度和脑血管功能障碍:对认知障碍和神经病理学的影响
基本信息
- 批准号:10724996
- 负责人:
- 金额:$ 1.97万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2020
- 资助国家:美国
- 起止时间:2020-04-15 至 2025-02-28
- 项目状态:未结题
- 来源:
- 关键词:Abeta synthesisAgingAlzheimer&aposs DiseaseAmyloid beta-ProteinAortaArteriesBlood VesselsBlood flowBrainCarotid ArteriesCerebrovascular CirculationCerebrovascular DisordersCerebrovascular systemClinical ResearchDiseaseFunctional disorderFutureGoalsImpaired cognitionImpairmentInterventionKnowledgeLate Onset Alzheimer DiseaseLeadLinkMemoryMemory impairmentMethodsOxidative StressPrevalencePreventionRoleSourceTimeTransgenic MiceVascular Endothelial Cellabeta accumulationage relatedarterial stiffnessattenuationcandidate identificationcerebral arterycerebrovascularmouse modelneuropathologynew therapeutic targetpharmacologicpressurepreventtranscriptome
项目摘要
PROJECT SUMMARY
As the prevalence of late-onset Alzheimer’s disease continues to increase, understanding the mechanistic
causes of this disease is becoming increasingly critical. Recent clinical studies have linked increased stiffness
of the large arteries to both impaired memory and Alzheimer’s disease. It is hypothesized that these relations
are a result of large artery stiffness-induced cerebrovascular dysfunction. Increased large artery stiffness leads
to greater pulsatility of pressure and blood flow in the cerebral vasculature, which is known to cause vascular
damage. Dysfunction of the cerebral arteries and microvasculature is associated with cognitive impairment and
greater Alzheimer’s disease-related neuropathology. Furthermore, amyloid-β (Aβ) induces cerebrovascular
damage, and cerebrovascular impairment increases Aβ accumulation, thus creating a vicious cycle of
cerebrovascular dysfunction and neuropathology. The goal of the proposed studies is to provide the first proof-
of-concept evidence that age-related increases in large artery stiffness, synergistically with greater Aβ
production, lead to cognitive impairment, neuropathology, and cerebrovascular dysfunction. To accomplish this
goal, we will employ transgenic mouse models of greater large artery stiffness and greater Aβ production, as
well as use a pharmacological intervention to prevent age-related increases in large artery stiffness. In Aim 1,
we will assess the effects of large artery stiffness, in combination with Aβ, on cognitive dysfunction and
Alzheimer’s disease-related neuropathology. In Aim 2, we will determine the effect of large artery stiffness, in
combination with Aβ, on cerebral blood flow and cerebral vascular reactivity and structural integrity. In Aim 3,
we will identify candidate mechanisms by which large artery stiffness and greater cerebral artery pulsatility lead
to cerebrovascular dysfunction. To do so, we will examine the role and source(s) of vascular oxidative stress,
as well as perform transcriptome analysis of cerebral arteries and microvascular endothelial cells. The
knowledge to be gained by completing the proposed aims will inform future studies to identify novel therapeutic
targets for the prevention or attenuation of late-onset Alzheimer’s disease.
项目总结
随着晚发性阿尔茨海默病的患病率持续增加,了解其发病机制
这种疾病的病因正变得越来越严重。最近的临床研究表明,僵硬程度增加
记忆受损和阿尔茨海默病的大动脉。据推测,这些关系
是大动脉僵硬引起的脑血管功能障碍的结果。大动脉僵硬导联增加
与脑血管中压力和血流的脉动性更强有关,这是已知引起血管
损坏。脑动脉和微血管功能障碍与认知障碍和
更严重的阿尔茨海默病相关神经病理学。此外,淀粉样蛋白β(Aβ)可诱导脑血管病变
损伤和脑血管损伤会增加β的积聚,从而造成恶性循环
脑血管功能障碍和神经病理学。拟议研究的目标是提供第一个证据-
Of-Concept证据表明,与年龄相关的大动脉僵硬增加与较大的Aβ协同作用
产生,导致认知障碍、神经病理和脑血管功能障碍。要做到这一点
目标,我们将使用大动脉僵硬和Aβ产生更多的转基因小鼠模型,如
并使用药物干预来防止与年龄相关的大动脉僵硬增加。在目标1中,
我们将评估大动脉僵硬联合Aβ对认知功能障碍和
阿尔茨海默病相关的神经病理学。在目标2中,我们将确定大动脉僵硬的影响
联合Aβ,对脑血流量和脑血管反应性及结构完整性的影响。在《目标3》中,
我们将确定大动脉僵硬和更大的脑动脉搏动性导致的候选机制
脑血管功能障碍。为此,我们将探讨血管氧化应激的作用和来源(S),
以及对大脑动脉和微血管内皮细胞进行转录组分析。这个
通过完成建议的目标而获得的知识将为未来的研究提供信息,以确定新的治疗方法
预防或减轻迟发性阿尔茨海默病的目标。
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 }}
Ashley Elizabeth Walker其他文献
Ashley Elizabeth Walker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('Ashley Elizabeth Walker', 18)}}的其他基金
Large artery stiffness and cerebrovascular dysfunction: Implications for cognitive impairment and neuropathology
大动脉僵硬度和脑血管功能障碍:对认知障碍和神经病理学的影响
- 批准号:
10374072 - 财政年份:2020
- 资助金额:
$ 1.97万 - 项目类别:
Large artery stiffness and cerebrovascular dysfunction: Implications for cognitive impairment and neuropathology
大动脉僵硬度和脑血管功能障碍:对认知障碍和神经病理学的影响
- 批准号:
9973881 - 财政年份:2020
- 资助金额:
$ 1.97万 - 项目类别:
Large artery stiffness and cerebrovascular dysfunction: Implications for cognitive impairment and neuropathology
大动脉僵硬度和脑血管功能障碍:对认知障碍和神经病理学的影响
- 批准号:
10562398 - 财政年份:2020
- 资助金额:
$ 1.97万 - 项目类别:
Large artery stiffness and cerebrovascular dysfunction: Implications for cognitive impairment and neuropathology
大动脉僵硬度和脑血管功能障碍:对认知障碍和神经病理学的影响
- 批准号:
10524709 - 财政年份:2020
- 资助金额:
$ 1.97万 - 项目类别:
Large artery stiffness and cerebrovascular dysfunction: Implications for cognitive impairment and neuropathology
大动脉僵硬度和脑血管功能障碍:对认知障碍和神经病理学的影响
- 批准号:
10771912 - 财政年份:2020
- 资助金额:
$ 1.97万 - 项目类别:
Large artery stiffness and cerebrovascular dysfunction: Implications for cognitive impairment and neuropathology
大动脉僵硬度和脑血管功能障碍:对认知障碍和神经病理学的影响
- 批准号:
10576844 - 财政年份:2020
- 资助金额:
$ 1.97万 - 项目类别:
Large artery stiffness and cerebrovascular dysfunction: Implications for cognitive impairment and neuropathology
大动脉僵硬度和脑血管功能障碍:对认知障碍和神经病理学的影响
- 批准号:
10771913 - 财政年份:2020
- 资助金额:
$ 1.97万 - 项目类别:
Inflammatory suppression of endothelial function with aging and habitual exercise
衰老和习惯性运动对内皮功能的炎症抑制
- 批准号:
7408790 - 财政年份:2008
- 资助金额:
$ 1.97万 - 项目类别:
Inflammatory suppression of endothelial function with aging and habitual exercise
衰老和习惯性运动对内皮功能的炎症抑制
- 批准号:
7663798 - 财政年份:2008
- 资助金额:
$ 1.97万 - 项目类别:
相似海外基金
Interplay between Aging and Tubulin Posttranslational Modifications
衰老与微管蛋白翻译后修饰之间的相互作用
- 批准号:
24K18114 - 财政年份:2024
- 资助金额:
$ 1.97万 - 项目类别:
Grant-in-Aid for Early-Career Scientists
The Canadian Brain Health and Cognitive Impairment in Aging Knowledge Mobilization Hub: Sharing Stories of Research
加拿大大脑健康和老龄化认知障碍知识动员中心:分享研究故事
- 批准号:
498288 - 财政年份:2024
- 资助金额:
$ 1.97万 - 项目类别:
Operating Grants
EMNANDI: Advanced Characterisation and Aging of Compostable Bioplastics for Automotive Applications
EMNANDI:汽车应用可堆肥生物塑料的高级表征和老化
- 批准号:
10089306 - 财政年份:2024
- 资助金额:
$ 1.97万 - 项目类别:
Collaborative R&D
Baycrest Academy for Research and Education Summer Program in Aging (SPA): Strengthening research competencies, cultivating empathy, building interprofessional networks and skills, and fostering innovation among the next generation of healthcare workers t
Baycrest Academy for Research and Education Summer Program in Aging (SPA):加强研究能力,培养同理心,建立跨专业网络和技能,并促进下一代医疗保健工作者的创新
- 批准号:
498310 - 财政年份:2024
- 资助金额:
$ 1.97万 - 项目类别:
Operating Grants
関節リウマチ患者のSuccessful Agingに向けたフレイル予防対策の構築
类风湿性关节炎患者成功老龄化的衰弱预防措施的建立
- 批准号:
23K20339 - 财政年份:2024
- 资助金额:
$ 1.97万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Life course pathways in healthy aging and wellbeing
健康老龄化和福祉的生命历程路径
- 批准号:
2740736 - 财政年份:2024
- 资助金额:
$ 1.97万 - 项目类别:
Studentship
I-Corps: Aging in Place with Artificial Intelligence-Powered Augmented Reality
I-Corps:利用人工智能驱动的增强现实实现原地老龄化
- 批准号:
2406592 - 财政年份:2024
- 资助金额:
$ 1.97万 - 项目类别:
Standard Grant
NSF PRFB FY 2023: Connecting physiological and cellular aging to individual quality in a long-lived free-living mammal.
NSF PRFB 2023 财年:将生理和细胞衰老与长寿自由生活哺乳动物的个体质量联系起来。
- 批准号:
2305890 - 财政年份:2024
- 资助金额:
$ 1.97万 - 项目类别:
Fellowship Award
虚弱高齢者のSuccessful Agingを支える地域課題分析指標と手法の確立
建立区域问题分析指标和方法,支持体弱老年人成功老龄化
- 批准号:
23K20355 - 财政年份:2024
- 资助金额:
$ 1.97万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
「ケア期間」に着目したbiological aging指標の開発
开发聚焦“护理期”的生物衰老指数
- 批准号:
23K24782 - 财政年份:2024
- 资助金额:
$ 1.97万 - 项目类别:
Grant-in-Aid for Scientific Research (B)