Administrative Supplement to Sleep Fragmentation and Alzheimer's Disease
睡眠碎片化和阿尔茨海默病的行政补充
基本信息
- 批准号:10555721
- 负责人:
- 金额:$ 15.3万
- 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:2020-08-01 至 2025-04-30
- 项目状态:未结题
- 来源:
- 关键词:Abeta clearanceAdministrative SupplementAffectAlzheimer&aposs DiseaseAlzheimer&aposs disease patientAmyloid beta-ProteinAnti-Inflammatory AgentsAstrocytesChronicCognitive deficitsCorrelative StudyDementiaDepositionDevelopmentDiseaseDisease ProgressionExhibitsFamilyFrequenciesHumanImpaired cognitionLifeLife StyleLinkMediatingMicrogliaModelingMoodsPersonal SatisfactionPhase I Clinical TrialsPostmenopauseRiskScheduleSleepSleep DeprivationSleep DisordersSleep FragmentationsSleep disturbancesSlow-Wave SleepSocietiesTemperatureWomanWorkabeta accumulationage relatedbasebeta amyloid pathologyimprovedmild cognitive impairmentmouse modelneuroinflammationneuropathologyneurotoxicnoise exposurenovel strategiesnovel therapeutic interventionsexsleep qualitysleep quantity
项目摘要
Chronic sleep disruption, resulting from work schedules, noise exposure, family obligations, sleep disorders, or
lifestyle choices, is a pervasive feature of contemporary life. Sleep problems affect up to 40% of AD patients,
may precede cognitive impairments by more than a decade, and worsen as the disease progresses. As well as
affecting mood and well-being, sleep disruption may drive the development of AD neuropathology for instance,
by reducing clearance of amyloid-β (Aβ) and by promoting a neurotoxic proinflammatory state involving
astrocytes and microglia. Sleep disruption can include reduced total sleep (sleep restriction [SR]), loss of deep
sleep (also known as slow-wave sleep [SWS], marked by large amplitude, low frequency electrical activity),
and fragmentation of sleep (SF) into shorter bouts. Fragmentation of the daily sleep-wake rhythm is associated
with greater risk of incident AD and earlier cognitive decline in older humans. In spite of these correlative
studies, whether or how chronic SF impacts the progression of AD has not been experimentally investigated.
SF may be a better model of the sleep disruption associated with AD than the traditional approach of SR. Our
studies of AD mouse models show that spontaneously occurring SF is associated with more severe Aβ
accumulation and that experimentally-induced SF leads to Aβ accumulation and neuroinflammation. Besides
SF, loss of SWS may exacerbate AD, and improving SWS may be beneficial in mild cognitive impairment
(MCI) or even in AD. Since sleep disruption adversely affects the development of AD-related neuropathology, it
is surprising that sleep enhancement (SE) strategies to consolidate sleep and increase SWS have not been
adequately explored to slow or reverse these effects. Our overall working hypothesis is that a change in the
quality of sleep, especially sleep fragmentation and loss of SWS, is more important than the quantity of sleep.
Further, we hypothesize that the mechanism underlying these effects is primarily neuroinflammation, at least in
part mediated by Aβ peptide deposition. We will use a unique, well-characterized mouse model, that exhibits
AD-related Aβ pathology, neuroinflammation, and cognitive deficits. This project has three specific aims: (1)
that SF will accelerate (and SE decelerate) AD progression; (2) that increases in Aβ accumulation mediates
SF-induced neuroinflammation, neuropathology, and cognitive decline; and (3) that increases in
neuroinflammation mediate SF-induced neuropathology and cognitive decline. We will use multiple novel
approaches, including thermoneutral temperature manipulation, and a unique anti-inflammatory compound that
has recently entered early stage clinical trials. Thus, these studies will elucidate the underlying mechanisms by
which sleep disruption is linked to AD and will lay the groundwork for new therapeutic strategies.
慢性睡眠中断,由工作安排、噪音暴露、家庭责任、睡眠障碍或
项目成果
期刊论文数量(0)
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{{ truncateString('ADAM D BACHSTETTER', 18)}}的其他基金
Drug repurposing for Alzheimer’s disease-related inflammation caused by a TBI
药物再利用,治疗 TBI 引起的阿尔茨海默病相关炎症
- 批准号:
10590132 - 财政年份:2023
- 资助金额:
$ 15.3万 - 项目类别:
Neuronal IL-1R1 Signaling in Mild Closed Head Injury
轻度闭合性头部损伤中的神经元 IL-1R1 信号转导
- 批准号:
10518172 - 财政年份:2022
- 资助金额:
$ 15.3万 - 项目类别:
Neuronal IL-1R1 Signaling in Mild Closed Head Injury
轻度闭合性头部损伤中的神经元 IL-1R1 信号转导
- 批准号:
10656547 - 财政年份:2022
- 资助金额:
$ 15.3万 - 项目类别:
Translational Approaches to Mitigate Enhanced Alzheimer’s Disease Risk Following a Mild TBI
减轻轻度 TBI 后阿尔茨海默病风险增加的转化方法
- 批准号:
10090757 - 财政年份:2021
- 资助金额:
$ 15.3万 - 项目类别:
Cell-Specific Actions of IL-1 / IL-1R1 Signaling Following Traumatic Brain Injury
脑外伤后 IL-1/IL-1R1 信号传导的细胞特异性作用
- 批准号:
10307112 - 财政年份:2018
- 资助金额:
$ 15.3万 - 项目类别:
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