Neuropathology, Biomarker & Genetics Core C

神经病理学，生物标志物

• 批准号: 10373918
• 负责人: JOHN Q. TROJANOWSKI
• 金额: $ 45.27万
• 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/10373918
• 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; Dementia with Lewy Bodies; 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; biomarker signature; brain tissue; cerebral atrophy; comorbidity; conformer; disease heterogeneity; epigenetic marker; genetic risk factor; genetic signature; 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.

CORE：神经病理学、生物标志物和遗传学核心C 核心负责人：John Q. Trojanowski;联合核心领导人：Alice Chen-Plotkin，Edward B.李和薇薇安娜 货车迪尔林 核心摘要/摘要 NIA U19中心的神经病理学、生物标志物和遗传学核心C“关于α-突触核蛋白菌株 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”研究。 医学（PSOM）银行和表征从临床评估收集的死后脑组织 阿尔茨海默病（AD）患者以及帕金森病（PD）患者，没有和有认知障碍， 在核心B中随访的痴呆（PDD）和路易体痴呆（DLB）患者， 研究项目I-IV。它还收集来自这些受试者的血浆、脑脊液（CSF）和DNA， 进行基因分型并处理基因分型数据。PD、PDD和DLB（称为路易体障碍或路易体病） LBD）以及多系统萎缩（MSA）是一系列以α-突触核蛋白病为特征的突触核蛋白病， 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的少突胶质细胞中的胶质细胞胞质内含物（GCI）。LB最常见 AD和LBD是最常见的衰老相关的神经退行性痴呆。 最近的研究结果表明，具有aSyn病理学的AD（AD+aSyn）和LBD的进展可以反映细胞凋亡。 病理性aSyn构象异构体或菌株在神经系统中向细胞扩散，随后进行性 并且有证据表明tau和aSyn相互交叉融合。因此，U19专注于 对AD+aSyn和LBD的进展以及病理性炎症的CNS细胞间扩散机制的影响 aSyn。项目I和II表明，MSA可能来自独特的aSyn GCI菌株（aSyn-GCI菌株）， 在少突胶质细胞中传播，并且不同于与神经元中的LB/LN连接的那些aSyn构象异构体 的LBD（aSyn-LB菌株）。因此，核心C将与项目I和项目II密切合作， 将分析病理性aSyn并且随后将它们的特征与表型， 生物标志物和遗传患者数据与项目III和IV合作。Core C支持U19 Center 通过对从核心B转诊进行尸检的AD/LBD患者实施尸检诊断标准， 收集这些患者的生物样本，并评估死前诊断的效用，包括研究 潜在的基因和生物标记核心C与所有核心/项目密切合作，以支持 该中心的使命是改进诊断方法，提供脑组织、生物液体和DNA样本， 宾夕法尼亚大学U19中心内外的调查人员。