Identifying the relationship between alcohol and Alzheimer's Disease
确定酒精与阿尔茨海默病之间的关系
基本信息
- 批准号:10706467
- 负责人:
- 金额:$ 34.33万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2022
- 资助国家:美国
- 起止时间:2022-09-20 至 2027-06-30
- 项目状态:未结题
- 来源:
- 关键词:AccountingAddressAffectAffectiveAgeAlcohol consumptionAlcohol dependenceAlcoholsAlzheimer&aposs DiseaseAlzheimer&aposs disease modelAlzheimer&aposs disease patientAlzheimer&aposs disease riskAmyloid beta-ProteinAreaBehaviorBehavioralBehavioral SymptomsBrainBrain regionCellsChronicClinical ResearchCognitiveCognitive deficitsConsumptionDataDementiaDepositionEmotionalEthanolFunctional disorderGuidelinesHeavy DrinkingHumanImpaired cognitionIncidenceIndividualInjectionsLocationMeasuresMemantineMusNMDA receptor antagonistNerve DegenerationNeurodegenerative DisordersNeurologic SymptomsNeuronsPre-Clinical ModelPreventive measurePreventive treatmentProcessRecording of previous eventsReportingRisk FactorsRoleSalineSenile PlaquesSeveritiesStainsStructureSymptomsSynapsesTestingTissuesTransgenic MiceTreatment EffectivenessWild Type Mousealcohol effectalcohol researchalcohol use disorderanxiety-like behaviorassociated symptomcognitive functioncognitive testingcohortdesigndrinkingearly onseteffective therapyexperimental studygraph theorymorris water mazemouse modelneural networkneuropathologynovelobject recognitionpre-clinical researchreduce symptomstargeted treatmenttherapeutic developmenttreatment guidelinestreatment strategyvaporyoung adult
项目摘要
Project Summary / Abstract
Alzheimer's disease (AD) is the most common neurodegenerative disease worldwide, accounting for
approximately half to two-thirds of all cases of dementia. It is associated with cognitive impairments and an
increase in β-amyloid plaque (Aβ) deposits. Moreover, alcohol use disorder (AUD) has been associated with
neurodegeneration and cognitive impairments, but the role of alcohol dependence on AD has been somewhat
controversial. Recent evidence suggests a likely role for alcohol use as a risk factor in onset and severity of
Alzheimer's disease, however overall reports have been mixed. Given the pervasive use of alcohol, it is critical
to understand the potential impact of alcohol drinking on AD. We will examine the impact of a history of alcohol
dependence on the onset and severity of behavioral and neuropathological symptoms associated with AD. We
will further examine how alcohol dependence influences neural network function in AD. We will assess whether
or not treatment with Memantine can reverse the behavioral and neuropathological symptoms. We hypothesize
that a history of alcohol dependence will result in an earlier onset of cognitive impairment in AD mice as well as
a greater presence of Aβ deposits and that these deficits will be rescued by chronic treatment with Memantine.
We hypothesize that a history of alcohol dependence in AD mice will alter network connectivity (decrease
modularity and change hub regions) and that these effects will be alleviated by Memantine treatment. Alterations
of functional network connectivity that are caused by alcohol dependence will be assessed in a mouse model of
AD. These changes will be compared with the brain-wide spread of Aβ deposits, which will indicate the way in
which AD affects brain-wide function, potentially beyond brain areas with signs of neuropathology. Furthermore,
the role of alcohol dependence in AD (e.g., changes in network connectivity and behavioral and
neuropathological symptoms) will be examined using a relevant translational preclinical model of AUD. Cognitive
function, anxiety-like behavior, and irritability-like behavior will be assessed in AD and wildtype alcohol drinking
and alcohol naive mice. The number and location of Aβ deposits will be assessed AD mice. Differences in
network connectivity in AD and wildtype mice will be examined using hierarchical clustering and graph theory. If
alcohol dependence is found to impact the onset of neurological and behavioral symptoms of AD, then this will
be a highly significant finding that will have a broad impact on preclinical and clinical research. These potential
findings may also directly influence public guidelines for alcohol consumption, especially in those with a familial
risk for AD.
项目摘要/摘要
阿尔茨海默病(AD)是世界上最常见的神经退行性疾病,占
大约一半到三分之二的痴呆症病例。它与认知障碍和
β-淀粉样斑块(A-β)沉积增加。此外,酒精使用障碍(AUD)与
神经退行性变和认知障碍,但酒精依赖对AD的作用在某种程度上
有争议的。最近的证据表明,饮酒可能是糖尿病发病和严重程度的危险因素。
然而,总体来说,关于阿尔茨海默氏症的报道喜忧参半。鉴于酒精的普遍使用,这一点至关重要
了解饮酒对阿尔茨海默病的潜在影响。我们将考察酗酒史的影响
依赖于与AD相关的行为和神经病理症状的开始和严重程度。我们
将进一步研究酒精依赖如何影响阿尔茨海默病的神经网络功能。我们将评估是否
无论是否使用美金刚治疗,都可以逆转行为和神经病理症状。我们假设
酒精依赖史会导致阿尔茨海默病小鼠以及
更多的Aβ沉积,这些缺陷将通过美金刚的长期治疗而得到挽救。
我们假设,阿尔茨海默病小鼠的酒精依赖史会改变网络连接(减少
模块化和改变枢纽区域),这些影响将通过美金刚处理得到缓解。改建
酒精依赖引起的功能网络连通性将在小鼠模型中进行评估
广告。这些变化将与Aβ存款在全脑范围内的分布进行比较,这将表明
哪种阿尔茨海默病会影响整个大脑的功能,可能超出了有神经病理迹象的大脑区域。此外,
酒精依赖在阿尔茨海默病中的作用(例如,网络连接和行为的改变
神经病理症状)将使用相关的AUD翻译前临床模型进行检查。认知
功能、焦虑样行为和易怒样行为将在AD和野性饮酒中进行评估
和酗酒的天真老鼠。Aβ沉积的数量和位置将被评估为AD小鼠。差异在于
AD和野生型小鼠的网络连通性将使用等级聚类和图论进行检查。如果
酒精依赖被发现会影响阿尔茨海默病的神经和行为症状的出现,然后这将
这是一项非常有意义的发现,将对临床前和临床研究产生广泛影响。这些潜力
研究结果还可能直接影响公众的饮酒指南,特别是在有家族史的人中
AD的风险。
项目成果
期刊论文数量(2)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Adam J Kimbrough其他文献
Adam J Kimbrough的其他文献
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{{ truncateString('Adam J Kimbrough', 18)}}的其他基金
Identifying the relationship between alcohol and Alzheimer's Disease
确定酒精与阿尔茨海默病之间的关系
- 批准号:
10412429 - 财政年份:2022
- 资助金额:
$ 34.33万 - 项目类别:
Network wide analysis of brain activity involved in alcohol withdrawal
酒精戒断相关大脑活动的网络范围分析
- 批准号:
10249381 - 财政年份:2018
- 资助金额:
$ 34.33万 - 项目类别:
Network wide analysis of brain activity involved in alcohol withdrawal
酒精戒断相关大脑活动的网络范围分析
- 批准号:
9646828 - 财政年份:2018
- 资助金额:
$ 34.33万 - 项目类别:
Network wide analysis of brain activity involved in alcohol withdrawal
酒精戒断相关大脑活动的网络范围分析
- 批准号:
10470857 - 财政年份:2018
- 资助金额:
$ 34.33万 - 项目类别:
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