Quantifying synaptic density loss in a monkey model of early Alzheimer's Disease
量化早期阿尔茨海默病猴子模型中的突触密度损失
基本信息
- 批准号:9809280
- 负责人:
- 金额:$ 30.88万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2019
- 资助国家:美国
- 起止时间:2019-08-01 至 2021-04-30
- 项目状态:已结题
- 来源:
- 关键词:AD pathologyAddressAgeAlzheimer&aposs DiseaseAlzheimer&aposs disease riskAmyloid beta-ProteinAmyloid depositionAnimalsAtlasesAttenuatedAutopsyBehavioralBiological MarkersBiological ModelsBlood - brain barrier anatomyBrainBrain PathologyBrain regionCerebrumClinical ResearchControl AnimalDNA Sequence AlterationDataDevelopmentDiagnosisDiagnosticDisease ProgressionDoseEarly DiagnosisElementsFollow-Up StudiesFunctional disorderFutureGoalsGoldHealthHistologicHumanImaging TechniquesImpaired cognitionInfusion proceduresIntervention StudiesInvestigationLongitudinal StudiesMRI ScansMacaca mulattaMagnetic Resonance ImagingMapsMeasurementMeasuresMetabolicMetabolic dysfunctionMethodsMicroscopicModelingMolecularMonkeysNeuronsNuclearPathogenesisPathologicPathologyPatientsPatternPeptidesPhasePositron-Emission TomographyProcessResearchResearch DesignRodentRoleSample SizeScanningSignal TransductionSpatial DistributionStructureSynapsesTestingTherapeuticTissuesTreatment EffectivenessValidationabeta oligomerbasebrain tissuecerebral atrophycostdensitydesigndisabling diseasefluorodeoxyglucosefluorodeoxyglucose positron emission tomographyfollow-upglucose metabolismimaging modalityimprovedin vivoin vivo imagingindexinginterestlateral ventriclemultimodalityneuropathologynonhuman primatenovelpreclinical studypredictive markerradiotracerresponseserial imagingsexspatiotemporaltau aggregationtherapeutic evaluationtherapy designtreatment strategy
项目摘要
Project Summary/Abstract
Alzheimer’s disease (AD) is an extremely prevalent and severely disabling disease. Despite several decades
of research, AD pathogenesis continues to be poorly understood, and we currently lack reliable biomarkers to
spatiotemporally track and predict disease progression. Our overall goal is to address these challenges and
develop enhanced biomarkers for diagnosing AD-pathology early and objectively tracking treatments. To that
end, this proposal will utilize our highly translational monkey model of the early “synaptic phase” of AD to
assess the merits of in vivo imaging measures (from PET for synaptic density (using 11C-UCB-J) and glucose
metabolism (using 18F-FDG), with structural MRI) against postmortem, state-of-the-art microscopic and
histologic analysis of brain tissue, in a longitudinal study design. Our hypothesis is that PET measures, as
surrogates for quantifying synaptic loss and metabolic dysfunction, will serve as early, independent predictive
biomarkers for elevated AD risk and cognitive dysfunction. Our first specific aim will establish the correlation of
our in vivo imaging measures with postmortem tissue markers of AD-associated pathologies in our monkey
model versus age- and sex-matched control animals. Our second specific aim will map the spatiotemporal
patterns of PET synaptic loss versus cerebral glucose metabolism in our monkey model versus control animals
over a 12-week period. Completion of both aims will provide novel data to improve our understanding of
synaptic neuropathology in AD development. Therefore, this proposal is highly responsive to the PAR-18-760.
Positive findings would corroborate recent human studies investigating the role of synaptic dysfunction as a
major factor for increased AD risk. Validation of in vivo imaging strategies in a relevant model system will
contribute towards (i) optimizing the therapeutic window for future early AD treatments so that their efficacy can
be maximized; (ii) testing mechanistic hypotheses associated with the role/blockage of synapse loss; (iii)
rapidly evaluating new treatment strategies and their dose-response relationships. In summary, this project has
the potential to provide key translational elements that will inform human studies evaluating in vivo markers of
synaptic dysfunction.
项目总结/文摘
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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Abhijit J Chaudhari其他文献
Beyond skin deep: total-body positron emission tomography to illuminate systemic inflammation in psoriatic arthritis
不仅仅是表面现象:全身正电子发射断层扫描揭示银屑病关节炎中的全身性炎症
- DOI:
10.1016/j.coi.2025.102587 - 发表时间:
2025-08-01 - 期刊:
- 影响因子:5.800
- 作者:
Abhijit J Chaudhari;Yasser G Abdelhafez;Lorenzo Nardo;Siba P Raychaudhuri - 通讯作者:
Siba P Raychaudhuri
Abhijit J Chaudhari的其他文献
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{{ truncateString('Abhijit J Chaudhari', 18)}}的其他基金
Multimodality PET/CT Scanner for Small Animal Imaging
用于小动物成像的多模态 PET/CT 扫描仪
- 批准号:
10429458 - 财政年份:2022
- 资助金额:
$ 30.88万 - 项目类别:
Total-body PET for assessing myofascial pain
用于评估肌筋膜疼痛的全身 PET
- 批准号:
10571508 - 财政年份:2022
- 资助金额:
$ 30.88万 - 项目类别:
Imaging biomarkers of early synaptic changes in a preclinical model of Alzheimer’s disease
阿尔茨海默病临床前模型中早期突触变化的成像生物标志物
- 批准号:
9980756 - 财政年份:2019
- 资助金额:
$ 30.88万 - 项目类别:
Total-Body PET/CT for assessing Rheumatoid Arthritis Disease Activity and Treatment Response
全身 PET/CT 用于评估类风湿性关节炎疾病活动性和治疗反应
- 批准号:
9817105 - 财政年份:2019
- 资助金额:
$ 30.88万 - 项目类别:
Total-Body PET/CT for assessing Rheumatoid Arthritis Disease Activity and Treatment Response
全身 PET/CT 用于评估类风湿性关节炎疾病活动性和治疗反应
- 批准号:
10220852 - 财政年份:2019
- 资助金额:
$ 30.88万 - 项目类别:
Imaging biomarkers of early synaptic changes in a preclinical model of Alzheimer’s disease
阿尔茨海默病临床前模型中早期突触变化的成像生物标志物
- 批准号:
9807999 - 财政年份:2019
- 资助金额:
$ 30.88万 - 项目类别:
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