Neuropathology, Biomarker & Genetics Core C

神经病理学，生物标志物

• 批准号: 10654796
• 负责人: JOHN Q. TROJANOWSKI
• 金额: $ 41.69万
• 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 2025-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10654796
• 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; Clinical assessments; Collaborations; Correlative Study; Cytoplasmic Inclusion; DNA; Data; Databases; Dementia; Dementia with Lewy Bodies; Diagnosis; Diagnostic; Diagnostic Procedure; Epigenetic Process; Freezing; Genetic; Genetic Risk; Genetic study; Genotype; Goals; 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; Neurodegenerative Disorders; Neurofibrillary Tangles; Neurons; Oligodendroglia; Parkinson Disease; Participant; Pathologic; Pathology; Patients; Pattern; Pennsylvania; Phenotype; 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; diagnostic criteria; disease heterogeneity; genetic risk factor; genetic signature; imaging modality; improved; medical schools; multimodality; neurodegenerative dementia; neuropathology; patient oriented; 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、生物标志物和遗传学 核心 C 核心领导者：John Q. Trojanowski 联合核心领导者：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，无论是否患有认知障碍 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 项目 I-IV 中的研究还收集了这些受试者的血浆、脑脊液 (CSF) 和 DNA， 执行基因分型，并处理 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) 是最常见的。 AD 的共同病理学，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，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 神经退行性疾病，并且有证据表明 tau 和 aSyn 相互交叉原纤维化，因此，该 U19 聚焦。 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 aSyn 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）， 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 因此，Core C 将与项目 I 和 II 密切合作，其中具有不同的菌株。 将分析病理性 aSyn，随后将其特征与表型相关联， 与 Projects III 和 IV 合作的生物标志物和遗传患者数据为 U19 中心提供支持。 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的核心 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、生物体液和 DNA 样本 宾夕法尼亚大学 U19 中心内外的调查员。