Impact of Chronic Seizures on Neuropsychiatric Comorbidities in AD-Associated Models
慢性癫痫发作对 AD 相关模型中神经精神合并症的影响
基本信息
- 批准号:10651660
- 负责人:
- 金额:$ 38.88万
- 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:2020-09-15 至 2025-05-31
- 项目状态:未结题
- 来源:
- 关键词:AccelerationAddressAffectAgeAlzheimer&aposs DiseaseAlzheimer&aposs disease modelAlzheimer&aposs disease pathologyAlzheimer&aposs disease patientAlzheimer&aposs disease riskAmyloid beta-ProteinAmyloid beta-Protein PrecursorAnxietyBehavioralCaregiversChronicClinicalClinical ResearchCorneaDNA Sequence AlterationDataDepositionDevelopmentDiseaseDisease ProgressionEarly Onset Alzheimer DiseaseEpilepsyEpileptogenesisEventExhibitsFocal SeizureFunctional disorderGenesGenotypeGoalsHippocampusImmediate-Early GenesImpact SeizuresIn VitroIncidenceInflammatoryKnockout MiceKnowledgeLanguageMeasuresMedicalMental DepressionModelingMolecularMusMutant Strains MiceMutationNatureNeuronal PlasticityPathologyPatientsPatternPre-Clinical ModelProcessProtein OverexpressionQuality of lifeReportingRisk FactorsRoleSeizuresSenile PlaquesSeveritiesSleep Wake CycleSleep disturbancesSynaptic plasticityTestingTransgenic MiceVariantWild Type MouseWorkabeta accumulationage relatedagedanxiety-like behaviorassociated symptomautosomebeta amyloid pathologyburden of illnesscircadiancomorbiditycytokineexperiencegenetic varianthyperphosphorylated taumolecular markerneuroinflammationneuropathologyneuropsychiatric symptomneuropsychiatryoverexpressionpre-clinicalpresenilinpresenilin-1presenilin-2protein expressionrisk variant
项目摘要
Abstract:
Autosomal dominant early-onset Alzheimer's disease (ADEOAD) is associated with numerous
genetic mutations, including those in amyloid precursor protein (APP), and presenilin (PSEN) 1
and 2 genes. Growing evidence indicates that patients with AD often experience undiagnosed
focal seizures. Indeed, over 30% of AD patients with the most common PSEN2 gene variant
(N141I) report seizures and patients with APP duplication have a similarly high incidence of
reported seizures, suggesting an unexplored role of hyperexcitability in the pathophysiology of
AD. Both epilepsy and AD are associated with numerous neuropsychiatric comorbidities.
Limited clinical evidence suggests that AD patients with reported seizures may have worsened
long-term disease trajectory. However, few studies have directly addressed how chronic
seizures in the presence of AD-associated risk genes affect long-term neuropsychiatric and
behavioral comorbidities. Even less data exists to directly define the age-dependent impact of
chronic seizures on neuroplasticity processes, which may also underlie neuropsychiatric
comorbidities of AD. This proposal will thus demonstrate how chronic seizures age-dependently
impact neuropsychiatric comorbidities and neuroplasticity-associated protein expression in
several preclinical models of AD that do and do not demonstrate amyloid-beta accumulation
(APP/PSEN1 and PSEN2-N141I, respectively). This proposal will definitively address whether
and when chronic seizures impact the functional and neuropathological sequelae of AD so as to
elucidate whether seizures are a contributor to worsened AD trajectory. It is currently unclear
when in the course of AD seizures occur. It is also unclear whether these seizures exacerbate
neuropsychiatric symptoms associated with AD. ADEOAD-risk genes represent underexplored
molecular contributors to network hyperexcitability, which may accelerate disease progression
in the context of AD. The major goal of this project is to thus define the age-dependent additive
impact of ADEOAD-associated risk factors and chronic seizures on the development and
severity of neuropsychiatric comorbidities and neuroplasticity-associated protein expression.
文摘:
项目成果
期刊论文数量(3)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Loss of normal Alzheimer's disease-associated Presenilin 2 function alters antiseizure medicine potency and tolerability in the 6-Hz focal seizure model.
- DOI:10.3389/fneur.2023.1223472
- 发表时间:2023
- 期刊:
- 影响因子:3.4
- 作者:
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Melissa Leigh Barker-Haliski其他文献
Melissa Leigh Barker-Haliski的其他文献
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{{ truncateString('Melissa Leigh Barker-Haliski', 18)}}的其他基金
Investigational WNT-pathway modulators for the treatment and prevention of drug-resistant seizures
用于治疗和预防耐药性癫痫发作的研究性 WNT 通路调节剂
- 批准号:
10725450 - 财政年份:2023
- 资助金额:
$ 38.88万 - 项目类别:
Impact of Chronic Seizures on Neuropsychiatric Comorbidities in AD-Associated Models
慢性癫痫发作对 AD 相关模型中神经精神合并症的影响
- 批准号:
10441520 - 财政年份:2020
- 资助金额:
$ 38.88万 - 项目类别:
Impact of Chronic Seizures on Neuropsychiatric Comorbidities in AD-Associated Models
慢性癫痫发作对 AD 相关模型中神经精神合并症的影响
- 批准号:
9895415 - 财政年份:2020
- 资助金额:
$ 38.88万 - 项目类别:
Impact of Chronic Seizures on Neuropsychiatric Comorbidities in AD-Associated Models
慢性癫痫发作对 AD 相关模型中神经精神合并症的影响
- 批准号:
10261356 - 财政年份:2020
- 资助金额:
$ 38.88万 - 项目类别:
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