The role of sex in GABAergic-mediated, Alzheimer’s disease-related episodic memory impairments from mid to late life
性在 GABA 能介导的、阿尔茨海默病相关的中晚年情景记忆障碍中的作用
基本信息
- 批准号:10693240
- 负责人:
- 金额:$ 81.09万
- 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:2022-09-01 至 2027-06-30
- 项目状态:未结题
- 来源:
- 关键词:AccountingAffectAgeAgingAllelesAlzheimer&aposs DiseaseAlzheimer&aposs disease modelAlzheimer&aposs disease riskAmericanAmyloid beta-ProteinAnimal ExperimentationAnimalsApolipoproteinsAreaBehavioralBiological AssayBrainBrain imagingClinicalClinical TrialsCognitiveCommunitiesDementiaDevelopmentDiagnosisDisparityElderlyEpisodic memoryEstradiolEstrogen declineEstrogensEventFemaleFunctional disorderGenetic RiskGonadal Steroid HormonesHippocampusHormonesHumanHyperactivityImpaired cognitionImpairmentIndividualIndividual DifferencesInhibitory SynapseInterneuronsInterventionLongevityMediatingMemoryMemory LossMemory impairmentMenopauseModelingMorphologyNeurobehavioral ManifestationsNeurobiologyNeurodegenerative DisordersNeuronsPathogenesisPathologyPatternPerimenopausePlayPositron-Emission TomographyPostmenopausePremenopauseProgesteroneQuality of lifeRiskRoleSamplingSex DifferencesSymptomsSystemTechniquesTestingWomanWorkabeta accumulationage relatedapolipoprotein E-4episodic memory impairmentgamma-Aminobutyric Acidgenetic risk factorhippocampal pyramidal neuronhuman femalehuman malehuman modelimprovedmalememory consolidationmenmiddle ageneural modelneurotoxicitynew therapeutic targetprecision medicinereceptorsexsteroid hormonesymposiumtheories
项目摘要
Project Summary
Alzheimer’s disease (AD) is a progressive neurodegenerative disorder that severely hinders quality of life. It is
the leading cause of dementia in the elderly, and disproportionately affects women. Not only are women more
likely to be diagnosed with AD, but when they are, they show steeper rates of episodic memory decline, the
hallmark clinical symptom of AD. Studies using animals have provided strong evidence that γ-aminobutyric
acid (GABA) plays a critical role in episodic memory by regulating neuronal activity in the hippocampus –a
brain area that undergoes morphologic and functional changes in aging and AD. Experimentally induced
estrogen depletion, again in studies in animals, results in reductions in GABA. Furthermore, it has been shown
that apolipoprotein ε4 –the strongest common genetic risk factor for AD– is particularly detrimental in females,
and exacerbates dysfunction of the GABAergic system. This proposal extends these findings to test a sex-
specific, biologically-based GABAergic model of neural and episodic memory impairments in humans. By
capitalizing upon recent technical advancements in brain imaging and sex steroid hormone assay techniques,
this project will directly test whether hippocampal GABA concentration impacts brain activity and episodic
memory in a community-dwelling sample of middle-aged and older adults at risk for developing AD. Further,
this project will be the first of its kind to focus on the consequences of the decreases in estrogen
accompanying menopause in human females for the GABAergic cascade. The results of this project will have
important implications for our understanding of the neurobiological basis of AD and its cognitive symptoms,
and may, in turn, spark new therapeutic targets of intervention.
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)
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Teal S Eich其他文献
Intact and impaired cognitive-control processes in schizophrenia
精神分裂症的认知控制过程完整和受损
- DOI:
- 发表时间:
2011 - 期刊:
- 影响因子:4.5
- 作者:
Edward E. Smith;Teal S Eich;Deniz Cebenoyan;C. Malapani - 通讯作者:
C. Malapani
Cognitive Control in Schizophrenia Teal S. Eich Submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy in the Graduate School of Arts and Sciences
精神分裂症的认知控制 Teal S. Eich 部分满足艺术与科学研究生院哲学博士学位的要求提交
- DOI:
- 发表时间:
2014 - 期刊:
- 影响因子:0
- 作者:
Teal S Eich - 通讯作者:
Teal S Eich
Teal S Eich的其他文献
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{{ truncateString('Teal S Eich', 18)}}的其他基金
The role of sex in GABAergic-mediated, Alzheimer’s disease-related episodic memory impairments from mid to late life
性在 GABA 能介导的、阿尔茨海默病相关的中晚年情景记忆障碍中的作用
- 批准号:
10540130 - 财政年份:2022
- 资助金额:
$ 81.09万 - 项目类别:
Exploring the Latent Class Structure of Inhibition in Normal Aging
探索正常衰老过程中抑制的潜在类别结构
- 批准号:
10217953 - 财政年份:2019
- 资助金额:
$ 81.09万 - 项目类别:
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