Neuropathology, Biomarker & Genetics Core C
神经病理学,生物标志物
基本信息
- 批准号:10452560
- 负责人:
- 金额:$ 100.1万
- 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:2019-09-30 至 2024-05-31
- 项目状态:已结题
- 来源:
- 关键词:AgingAlzheimer&aposs DiseaseAlzheimer&aposs disease diagnosisAlzheimer&aposs disease pathologyAlzheimer&aposs disease patientAlzheimer&aposs disease related dementiaAmyloidAmyloid beta-ProteinArchivesAutopsyBiological MarkersBiometryBrainBrain-Derived Neurotrophic FactorCellsCerebrospinal FluidClinicalCollaborationsCorrelative StudyCytoplasmic InclusionDNADataDatabasesDementiaDementia with Lewy BodiesDiagnosisDiagnosticDiagnostic ProcedureFreezingGeneticGenetic MarkersGenetic RiskGenetic studyGenotypeGoalsImageImpaired cognitionLewy BodiesLewy Body DementiaLewy Body DiseaseLewy neuritesLinkMeasurableMethodsMissionMonitorMultiple System AtrophyMutationNerve DegenerationNervous system structureNeurodegenerative DisordersNeurofibrillary TanglesNeuronsOligodendrogliaParkinson DiseaseParticipantPathologicPathologyPatientsPatternPennsylvaniaPlasmaPlayProcessResearchResearch DesignResearch PersonnelResourcesRoleSNCA geneSamplingScientistSenile PlaquesTissuesTrainingUniversitiesVariantWorkalpha synucleinbiomarker signaturebrain tissuecerebral atrophycomorbidityconformerdiagnostic criteriadisease heterogeneityepigenetic markergenetic risk factorgenetic signatureimprovedmedical schoolsmultimodalityneurodegenerative dementianeuropathologypatient orientedphenotypic biomarkerpreservationprogramsprogressive neurodegenerationrisk variantsynucleinopathytau Proteins
项目摘要
CORE: Neuropathology, Biomarker & Genetics Core C
Core Leader: John Q. Trojanowski; Co-Core Leaders: Alice Chen-Plotkin, Edward B. Lee and Vivianna
Van Deerlin
Core Summary/Abstract
The Neuropathology, Biomarker and Genetics Core C in this NIA U19 “ Center On Alpha-synuclein Strains
In Alzheimer Disease & Related Dementias” at the University of Pennsylvania (Penn) Perelman School of
Medicine (PSOM) banks and characterizes postmortem brain tissue collected from clinically assessed
Alzheimer's disease (AD) patients as well as Parkinson's disease (PD) patients without and with cognitive
impairments (CI) or dementia (PDD) and dementia with Lewy body (DLB) patients followed in Core B and
studied in Projects I-IV. It also collects plasma, cerebrospinal fluid (CSF) and DNA from these subjects,
performs genotyping, and handles genotyping data. PD, PDD and DLB (referred to as Lewy body disorders or
LBD) as well as multiple system atrophy (MSA) are a spectrum of synucleinopathies characterized by alpha-
synuclein (aSyn) aggregates in neurons referred to as Lewy bodies (LBs) and Lewy neurites (LNs) in
PD/PDD/DLB or as glial cytoplasmic inclusions (GCIs) in oligodendrocytes of MSA. LBs are the most common
co-pathology in AD while AD and LBD are the most common aging related neurodegenerative dementias.
Recent findings suggest that progression of AD with aSyn pathology (AD+aSyn) and LBD could reflect the cell-
to-cell spread of pathological aSyn conformers or strains in the nervous system followed by progressive
neurodegeneration and there is evidence that tau and aSyn cross-fibrillize each other. Thus, this U19 focuses
on the progression of AD+aSyn and LBD as well as mechanisms of CNS cell-to-cell spread of pathological
aSyn. Projects I and II showed that MSA may result from a unique aSyn GCI strain (aSyn-GCI strain) that
spreads among oligodendroglial cells and is distinct from those aSyn conformers linked to LBs/LNs in neurons
of LBD (aSyn-LB strain). Hence, Core C will work closely with Projects I and II wherein distinct strains of
pathological aSyn will be analyzed and their features will subsequently be associated with phenotypic,
biomarker and genetic patient data in collaboration with Projects III and IV. Core C supports the U19 Center
goals by implementing postmortem diagnostic criteria for AD/LBD patients referred for autopsy from Core B,
collecting biosamples from these patients and assessing the utility of antemortem diagnostics including studies
of potential genetic and biomarker signatures. Core C works closely with all Cores/Projects to support the
Center's mission by improving diagnostic methods, and providing samples of brain tissue, biofluids and DNA to
investigators within and beyond the Penn U19 Center.
核心:神经病理学、生物标志物和遗传学 核心 C
核心领导人:John Q. Trojanowski;共同核心领导者:Alice Chen-Plotkin、Edward B. Lee 和 Vivianna
范迪尔林
核心摘要/摘要
NIA U19“α-突触核蛋白菌株中心”中的神经病理学、生物标志物和遗传学核心 C
宾夕法尼亚大学佩雷尔曼学院的“阿尔茨海默病及相关痴呆症”
医学 (PSOM) 存储并表征从临床评估中收集的死后脑组织
阿尔茨海默病 (AD) 患者以及帕金森病 (PD) 患者(无认知功能和有认知功能)
核心 B 和路易体痴呆 (DLB) 患者遵循损伤 (CI) 或痴呆 (PDD) 和痴呆 (DLB) 患者
参与项目 I-IV 的研究。它还收集这些受试者的血浆、脑脊液 (CSF) 和 DNA,
执行基因分型并处理基因分型数据。 PD、PDD 和 DLB(称为路易体疾病或
LBD)以及多系统萎缩(MSA)是一系列突触核蛋白病,其特征是 α-
突触核蛋白 (aSyn) 聚集在称为路易体 (LB) 和路易神经突 (LN) 的神经元中
PD/PDD/DLB 或 MSA 少突胶质细胞中的胶质细胞质内含物 (GCI)。 LB是最常见的
AD 和 LBD 是最常见的与衰老相关的神经退行性痴呆。
最近的研究结果表明,具有 aSyn 病理学 (AD+aSyn) 和 LBD 的 AD 进展可能反映了细胞-
神经系统中病理性 aSyn 构象异构体或菌株向细胞扩散,随后进行性
神经退行性变,并且有证据表明 tau 和 aSyn 相互交叉原纤维化。因此,本次U19重点
AD+aSyn 和 LBD 的进展以及病理性中枢神经系统细胞间传播的机制
一个同步。项目 I 和 II 表明 MSA 可能源自一种独特的 aSyn GCI 菌株(aSyn-GCI 菌株),该菌株
在少突胶质细胞中传播,与神经元中与 LB/LN 连接的 aSyn 构象不同
LBD(aSyn-LB 菌株)。因此,核心 C 将与项目 I 和 II 密切合作,其中不同的菌株
将分析病理性 aSyn,随后将其特征与表型相关联,
与项目 III 和 IV 合作的生物标志物和遗传患者数据。 Core C支持U19中心
通过对核心 B 转介进行尸检的 AD/LBD 患者实施尸检诊断标准来实现目标,
从这些患者身上收集生物样本并评估生前诊断(包括研究)的效用
潜在的遗传和生物标志物特征。 Core C 与所有核心/项目密切合作,以支持
中心的使命是改进诊断方法,并提供脑组织、生物体液和 DNA 样本
宾夕法尼亚大学 U19 中心内外的调查员。
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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JOHN Q. TROJANOWSKI其他文献
JOHN Q. TROJANOWSKI的其他文献
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{{ truncateString('JOHN Q. TROJANOWSKI', 18)}}的其他基金
Project II "aSyn Strains & Diverse Synucleinopathies"
项目二“aSyn菌株
- 批准号:
10020335 - 财政年份:2019
- 资助金额:
$ 100.1万 - 项目类别:
Project II "aSyn Strains & Diverse Synucleinopathies"
项目二“aSyn菌株
- 批准号:
10452563 - 财政年份:2019
- 资助金额:
$ 100.1万 - 项目类别:
Project II "aSyn Strains & Diverse Synucleinopathies"
项目二“aSyn菌株
- 批准号:
10654805 - 财政年份:2019
- 资助金额:
$ 100.1万 - 项目类别: