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
基本信息
- 批准号:9980756
- 负责人:
- 金额:$ 15.7万
- 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 2022-04-30
- 项目状态:已结题
- 来源:
- 关键词:AddressAffectAgeAge-MonthsAlzheimer&aposs DiseaseAlzheimer&aposs disease brainAlzheimer&aposs disease modelAlzheimer&aposs disease pathologyAlzheimer&aposs disease patientAlzheimer&aposs disease riskAlzheimer’s disease biomarkerAmericanAmyloid depositionAnimalsAstrocytesAtlasesBiological MarkersBrainCharacteristicsClinicalClinical TrialsControl AnimalDataDementiaDetectionDiseaseDisease ManagementDisease ProgressionDoseEarly DiagnosisElementsFunctional disorderFutureGliosisGoalsGoldHippocampus (Brain)HistologicHistologyHistopathologyHumanImageImpaired cognitionIn VitroIndividualInflammationMRI ScansMagnetic Resonance ImagingMapsMeasurementMeasuresMethodsMicrogliaModelingMonitorMotivationNeocortexNerve DegenerationNeurofibrillary TanglesNeurologicNeuronsOnset of illnessOutcomePathologicPathologyPatternPositron-Emission TomographyPre-Clinical ModelProcessProxyRattusResearchResearch DesignRiskRoleScanningSenile PlaquesSensitivity and SpecificitySignal TransductionStructureSynapsesTauopathiesTestingTherapeuticTimeTransgenic Organismsabeta accumulationabeta depositionage relatedbasecerebral amyloidosiscerebral atrophyclinical translationcongenicdensitydesignearly detection biomarkersevidence baseimage registrationimaging biomarkerimprovedin vivoin vivo imaginginsightneuron lossnovelnovel therapeutic interventionnovel therapeuticspredictive markerpreservationradiotracerresponserisk variantsocietal costsspatiotemporalstatisticstau Proteinstau aggregationtherapy designtool
项目摘要
Abstract
Alzheimer’s disease (AD) affects an estimated 5.7 million Americans, a number expected to reach 14 million by
2050. Despite several decades of research, the initiation and progression of AD continues to be poorly
understood, and we currently lack reliable biomarkers to longitudinally monitor disease progression. Synaptic
dysfunction is being evaluated as a potential early biomarker for evaluating AD risk; however, most studies to
date have relied on cross-sectional or endpoint, ex vivo analyses. We hypothesize that in vivo imaging
measures of synapse density, which will be carefully validated against histologic measures, will be predictive
biomarkers of AD pathology that precede detection of amyloid deposition and neurofibrillary tangles by in vivo
imaging. A positive outcome from testing this hypothesis would enable the identification of at-risk individuals
and the application of therapeutic strategies to arrest disease progression before substantial neuronal loss
occurs. Our studies will utilize PET and MR imaging in a novel transgenic rat model that presents key
pathologic features of significance in human AD. Our first specific aim will establish the spatial correlation
between in vivo imaging measures (synapse density, amyloid deposition and tauopathy via PET and structural
measures via MRI) and concurrent histopathology in the Tg344-AD transgenic rat model versus congenic age-
matched wildtype animals. Our second specific aim will map the spatiotemporal patterns of synapse density,
amyloid deposition, tauopathy and neurodegeneration via in vivo PET and MRI in TgF344-AD rats and age-
matched control animals. PET using the radiotracers 18F-UCB-H, 18F-florbetapir and 18F-T807, as proxy
measures of synapse density, amyloid-beta deposition and tau accumulation, respectively, and structural MRI,
based on T2-weighted scanning, will be performed over the time course of presentation of synaptic and AD-
related pathology. Brains from a subset of animals at each time will be analyzed for histopathologic markers of
neuronal loss and degeneration to provide ground-truth measures for correlating with the in vivo imaging
measures. This study will unleash the potential to: (i) robustly validate in vivo imaging measures of synapse
dysfunction as early biomarkers of AD against other imaging measures and histopathology, which is a
necessary step towards their evidence-based clinical translation; (ii) provide preliminary data to support future
mechanistic hypotheses about the regional and temporal relationships between synapse dysfunction and other
AD-associated pathologies, with the ultimate goal of improving our understanding of AD risk; and (iii)
understand concordance and discordance between the different in vivo imaging and histopathology measures,
which will have implications for therapy design and testing. In summary, this project will provide key
translational elements that will inform future human studies assessing the role of synapse loss in AD and for
monitoring treatments to preserve synapse density and function.
摘要
项目成果
期刊论文数量(0)
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科研奖励数量(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
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- 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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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:
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量化早期阿尔茨海默病猴子模型中的突触密度损失
- 批准号:
9809280 - 财政年份:2019
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$ 15.7万 - 项目类别:
Total-Body PET/CT for assessing Rheumatoid Arthritis Disease Activity and Treatment Response
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- 批准号:
10220852 - 财政年份:2019
- 资助金额:
$ 15.7万 - 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:
$ 15.7万 - 项目类别:
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