Effect of Suvorexant on Alzheimer's Disease Biomarkers

Suvorexant 对阿尔茨海默病生物标志物的影响

基本信息

  • 批准号:
    10584093
  • 负责人:
  • 金额:
    $ 159.55万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2023
  • 资助国家:
    美国
  • 起止时间:
    2023-04-15 至 2028-03-31
  • 项目状态:
    未结题

项目摘要

PROJECT SUMMARY Sleep disturbances are increasingly recognized as a risk factor for Alzheimer’s disease (AD) and a marker for Alzheimer’s disease pathology. The sleep-wake cycle affects the cerebrospinal fluid (CSF) concentrations of proteins critical to Alzheimer’s disease pathogenesis. We recently reported that overnight sleep disruption increases CSF amyloid-β (Aβ) levels by ~30% via increased production/release. Orexins (also called hypocretins) are wake-promoting neuropeptides. Chronic administration of a dual orexin receptor antagonist (DORA) to increase sleep in amyloid precursor protein (APP) transgenic mice decreased both the soluble concentration of Aβ in interstitial fluid and amyloid plaque formation. Our preliminary data shows that a DORA, suvorexant, acutely decreases the ratio of phosphorylated tau-181 (pT181) to unphosphorylated tau-181 (T181) in CSF. Although previous studies examined sleep-mediated changes in CSF Aβ and tau over hours, it is unknown how chronic administration of DORAs affect plasma and CSF tau, phosphorylated tau (p-tau), Aβ, and other Alzheimer’s disease fluid biomarkers in individuals with Alzheimer’s pathology. In this project, we will test the hypothesis that chronic treatment with suvorexant for 6 months will decrease CSF pT181/T181 and other CSF and plasma AD biomarkers. In this project, we will use an innovative adaptive trial design to test the potential of chronic treatment with suvorexant for secondary prevention of Alzheimer’s disease. 200 cognitively normal, amyloid-positive adults with symptomatic insomnia age ≥65 years will be randomized to receive placebo or suvorexant for 6 months. Each participant will undergo polysomnography as well as lumbar and venous puncture to sample CSF and blood at baseline, 3 months, and 6 months. We will test the hypothesis that chronic treatment with suvorexant will decrease CSF pT181/T181 as well as determine the effect on CSF plasma Aβ, CSF and plasma tau, other forms of CSF and plasma p-tau, and CSF markers for immune response (microglial function), synaptic function, and non-tau measures of neuronal degeneration. Optimal trial design is essential prior to launching a full secondary prevention trial with a maximum chance of success. This study will provide critical information for designing Alzheimer’s disease secondary prevention trial using suvorexant obtaining data on pharmacokinetics, safety, and chronic effects of suvorexant on multiple soluble Alzheimer’s disease biomarkers.
项目总结

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 }}

Brendan Patrick Lucey其他文献

Brendan Patrick Lucey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('Brendan Patrick Lucey', 18)}}的其他基金

Characterization of Orexin/Hypocretin Kinetics in Alzheimer's Disease
阿尔茨海默病中食欲素/下丘脑分泌素动力学的表征
  • 批准号:
    10491248
  • 财政年份:
    2021
  • 资助金额:
    $ 159.55万
  • 项目类别:
Characterization of Orexin/Hypocretin Kinetics in Alzheimer's Disease
阿尔茨海默病中食欲素/下丘脑分泌素动力学的表征
  • 批准号:
    10300328
  • 财政年份:
    2021
  • 资助金额:
    $ 159.55万
  • 项目类别:
Sleep Quality and Human Amlyoid-Beta Kinetics
睡眠质量和人类β淀粉样蛋白动力学
  • 批准号:
    9927556
  • 财政年份:
    2016
  • 资助金额:
    $ 159.55万
  • 项目类别:
SLEEP QUALITY AND HUMAN AMLYOID-BETA KINETICS
睡眠质量和人类淀粉样蛋白-β 动力学
  • 批准号:
    9934836
  • 财政年份:
    2016
  • 资助金额:
    $ 159.55万
  • 项目类别:
SLEEP: A POTENTIAL NOVEL MODULATOR OF ALZHEIMER'S DISEASE PATHOLOGY
睡眠:阿尔茨海默病病理学的潜在新型调节剂
  • 批准号:
    8755446
  • 财政年份:
    2014
  • 资助金额:
    $ 159.55万
  • 项目类别:
Sleep and Orexin: Potential Markers of Progression from Preclinical to Mildly Symptomatic Alzheimer's Disease
睡眠和食欲素:从临床前到轻度症状阿尔茨海默病进展的潜在标志
  • 批准号:
    10622500
  • 财政年份:
    1997
  • 资助金额:
    $ 159.55万
  • 项目类别:
Sleep and Orexin: Potential Markers of Progression from Preclinical to Mildly Symptomatic Alzheimer's Disease
睡眠和食欲素:从临床前到轻度症状阿尔茨海默病进展的潜在标志
  • 批准号:
    10396450
  • 财政年份:
    1997
  • 资助金额:
    $ 159.55万
  • 项目类别:
Sleep and Orexin: Potential Markers of Progression from Preclinical to Mildly Symptomatic Alzheimer's Disease
睡眠和食欲素:从临床前到轻度症状阿尔茨海默病进展的潜在标志
  • 批准号:
    9914186
  • 财政年份:
  • 资助金额:
    $ 159.55万
  • 项目类别:

相似海外基金

Co-designing a lifestyle, stop-vaping intervention for ex-smoking, adult vapers (CLOVER study)
为戒烟的成年电子烟使用者共同设计生活方式、戒烟干预措施(CLOVER 研究)
  • 批准号:
    MR/Z503605/1
  • 财政年份:
    2024
  • 资助金额:
    $ 159.55万
  • 项目类别:
    Research Grant
Early Life Antecedents Predicting Adult Daily Affective Reactivity to Stress
早期生活经历预测成人对压力的日常情感反应
  • 批准号:
    2336167
  • 财政年份:
    2024
  • 资助金额:
    $ 159.55万
  • 项目类别:
    Standard Grant
RAPID: Affective Mechanisms of Adjustment in Diverse Emerging Adult Student Communities Before, During, and Beyond the COVID-19 Pandemic
RAPID:COVID-19 大流行之前、期间和之后不同新兴成人学生社区的情感调整机制
  • 批准号:
    2402691
  • 财政年份:
    2024
  • 资助金额:
    $ 159.55万
  • 项目类别:
    Standard Grant
Migrant Youth and the Sociolegal Construction of Child and Adult Categories
流动青年与儿童和成人类别的社会法律建构
  • 批准号:
    2341428
  • 财政年份:
    2024
  • 资助金额:
    $ 159.55万
  • 项目类别:
    Standard Grant
Elucidation of Adult Newt Cells Regulating the ZRS enhancer during Limb Regeneration
阐明成体蝾螈细胞在肢体再生过程中调节 ZRS 增强子
  • 批准号:
    24K12150
  • 财政年份:
    2024
  • 资助金额:
    $ 159.55万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Understanding how platelets mediate new neuron formation in the adult brain
了解血小板如何介导成人大脑中新神经元的形成
  • 批准号:
    DE240100561
  • 财政年份:
    2024
  • 资助金额:
    $ 159.55万
  • 项目类别:
    Discovery Early Career Researcher Award
RUI: Evaluation of Neurotrophic-Like properties of Spaetzle-Toll Signaling in the Developing and Adult Cricket CNS
RUI:评估发育中和成年蟋蟀中枢神经系统中 Spaetzle-Toll 信号传导的神经营养样特性
  • 批准号:
    2230829
  • 财政年份:
    2023
  • 资助金额:
    $ 159.55万
  • 项目类别:
    Standard Grant
Usefulness of a question prompt sheet for onco-fertility in adolescent and young adult patients under 25 years old.
问题提示表对于 25 岁以下青少年和年轻成年患者的肿瘤生育力的有用性。
  • 批准号:
    23K09542
  • 财政年份:
    2023
  • 资助金额:
    $ 159.55万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Identification of new specific molecules associated with right ventricular dysfunction in adult patients with congenital heart disease
鉴定与成年先天性心脏病患者右心室功能障碍相关的新特异性分子
  • 批准号:
    23K07552
  • 财政年份:
    2023
  • 资助金额:
    $ 159.55万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Issue identifications and model developments in transitional care for patients with adult congenital heart disease.
成人先天性心脏病患者过渡护理的问题识别和模型开发。
  • 批准号:
    23K07559
  • 财政年份:
    2023
  • 资助金额:
    $ 159.55万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了