Neuropathology, Biomarker & Genetics Core C

神经病理学，生物标志物

• 批准号: 10020332
• 负责人: JOHN Q. TROJANOWSKI
• 金额: $ 41.56万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 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: https://reporter.nih.gov/project-details/10020332
• 关键词: Aging; Alzheimer' s Disease; Alzheimer' s disease diagnosis; Alzheimer' s disease pathology; Alzheimer' s disease patient; Alzheimer' s disease related dementia; Amyloid; Amyloid beta-Protein; Archives; Autopsy; Biological Markers; Biometry; Brain; Brain-Derived Neurotrophic Factor; Cells; Cerebrospinal Fluid; Clinical; Collaborations; Correlative Study; Cytoplasmic Inclusion; DNA; Data; Databases; Dementia; Diagnosis; Diagnostic; Diagnostic Procedure; Freezing; Genetic; Genetic Markers; Genetic Risk; Genetic study; Genotype; Goals; Image; Impaired cognition; Lewy Bodies; Lewy Body Dementia; Lewy Body Disease; Lewy neurites; Link; Measurable; Methods; Mission; Monitor; Multiple System Atrophy; Mutation; Nerve Degeneration; Nervous system structure; Neurodegenerative Disorders; Neurofibrillary Tangles; Neurons; Oligodendroglia; Parkinson Disease; Participant; Pathologic; Pathology; Patients; Pattern; Pennsylvania; Plasma; Play; Process; Research; Research Design; Research Personnel; Resources; Role; SNCA gene; Sampling; Scientist; Senile Plaques; Tissues; Training; Universities; Variant; Work; alpha synuclein; brain tissue; cerebral atrophy; comorbidity; conformer; disease heterogeneity; epigenetic marker; genetic risk factor; improved; medical schools; multimodality; neurodegenerative dementia; neuropathology; patient oriented; phenotypic biomarker; preservation; programs; progressive neurodegeneration; risk variant; synucleinopathy; tau Proteins

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、生物标记物和遗传学 核心领导人：John Q.Trojanowski；共同核心领导人：Alice Chen-Plotkin、Edward B.Lee和Vivianna 范德林 核心摘要/摘要 NIA U19“α-突触核蛋白中心的神经病理、生物标记物和遗传学核心C 宾夕法尼亚大学佩雷尔曼学院《阿尔茨海默病及相关痴呆》 医学(PSOM)库和特征从临床评估收集的尸检脑组织 阿尔茨海默病(AD)患者以及无认知和有认知障碍的帕金森病(PD)患者 损害(CI)或痴呆(PDD)和路易体痴呆(DLB)患者紧随核心B和 在项目I-IV中学习。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(称为路易体病或 LBD)和多系统萎缩(MSA)是一种以阿尔法-阿尔茨海默病为特征的联体核病 突触核蛋白(ASyn)聚集在神经元中，称为路易体(LBS)和路易神经节(LNS)。 PD/PDD/DLB或以胶质细胞胞质内包涵体形式存在于MSA的少突胶质细胞中。Lb是最常见的 AD的共同病理，而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，伴有aSyn病理的AD的进展(AD+aSyn)和LBD可以反映细胞- 病理性aSyn异构体或菌株在神经系统中向细胞扩散，随后是进行性 神经退化，有证据表明tau和aSyn相互交叉。因此，这款U19聚焦于 AD+aSyn和LBD的进展及CNS病理性细胞间扩散机制的研究 ASyn。项目I和项目II表明，MSA可能是由一种独特的aSyn GCI株(aSyn-GCI株)引起的 在少突胶质细胞中扩散，不同于神经元中与LBS/LNS连锁的aSyn构象 LBD(aSyn-Lb株)。因此，核心C将与项目I和项目II密切合作，在这些项目中， 病理性aSyn将被分析，其特征随后将与表型相关， 与项目III和项目IV合作的生物标志物和遗传患者数据。核心C支持U19中心 目标通过实施核心B中转诊的AD/LBD患者的死后诊断标准， 收集这些患者的生物样本，评估包括研究在内的生前诊断的有效性 潜在的遗传和生物标记物特征。核心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、生物液和DNA样本 宾夕法尼亚大学U19中心内外的调查人员。