South Texas Alzheimer's Disease Center Neuropathology Core

南德克萨斯阿尔茨海默病中心神经病理学核心

• 批准号: 10662354
• 负责人: Kevin F Bieniek
• 金额: $ 28.7万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-01 至 2026-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10662354
• 关键词: ATAC-seq; Address; Alzheimer' s Disease; Alzheimer' s disease related dementia; Amyloid beta-Protein; Archives; Area; Attention; Autopsy; Bar Codes; Basic Science; Behavior; Biological Markers; Brain; Brain region; Central Nervous System; Cerebrospinal Fluid; Cerebrovascular Trauma; Cities; Classification; Clinic; Clinical; Clinical assessments; Cognitive; Communities; Comprehensive Health Care; DNA; DNA analysis; Data; Data Set; Databases; Dementia; Diagnosis; Diagnostic; Disease; Dissection; Doctor of Philosophy; Education; Epigenetic Process; Ethnic Population; Etiology; Evaluation; Family; Fostering; Freezing; Future; Gene Expression; Genetic; Genetic Counseling; Genetic Polymorphism; Genetic Variation; Genomics; Glial Fibrillary Acidic Protein; Goals; Hematoxylin and Eosin Staining Method; Heterogeneity; Hispanic; Hispanic Americans; Hispanic Populations; Histology; Human Resources; Image; Individual; Institution; Interview; Liquid substance; Magnetic Resonance Imaging; Medical Genetics; Medical Records; Messenger RNA; Methodology; Methylation; Mexican Americans; Mission; Molecular; Natural History; Nerve Degeneration; Neuroanatomy; Neurodegenerative Disorders; Neurosciences; Neurosciences Research; Not Hispanic or Latino; Outcome; Participant; Pathogenesis; Pathologic; Pathology; Patients; Persons; Plasma; Population; Proteomics; Protocols documentation; RNA; Research; Research Personnel; Research Project Grants; Resources; Role; Sampling; Scanning; Scientist; Services; Skin; Slide; South Texas; Spinal Cord; Stains; Standardization; Students; System; Texas; Thioflavin S; Tissues; Training; Transcript; Translational Research; Traumatic Brain Injury; United States; Variant; aging brain; alpha synuclein; biobank; brain tissue; cerebrovascular; clinical diagnosis; cohort; cost; data management; demented; digital; digital pathology; education research; endophenotype; ethnic diversity; ethnoracial; exome sequencing; experimental study; frontotemporal lobar dementia amyotrophic lateral sclerosis; genetic testing; genomic data; hispanic community; histological stains; induced pluripotent stem cell; interest; metabolomics; metropolitan; multidisciplinary; multiple omics; nano-string; neurofilament; neuropathology; normal aging; novel; outreach; population based; pre-clinical; precision medicine; preservation; protein TDP-43; protein biomarkers; racial diversity; recruit; repository; statistics; tau Proteins; trait; transcriptomics

Understanding the complexity of heterogeneous and intersecting neurodegenerative disorders entails comprehensive qualitative and quantitative assessment of the central nervous system. Hence, the Neuropathology Core (NPC) is a pivotal component of the South Texas Alzheimer Center (STAC). Co-led by Kevin Bieniek, PhD and Jamie Walker, MD PhD, both trained especially for establishing and leading a new Brain Bank, this core comprehensively characterizes brain and spinal cord confirming clinical diagnoses, for purposes of research, and to provide a diagnosis and advice to families. Future advancements in elucidating and intervening in the pathogenesis of Alzheimer’s disease and related dementias (ADRD) requires the study of diverse ethnoracial autopsy cohorts. The STAC NPC services a large Mexican-American Hispanic population in the South Texas region. It will generate normative (cognitively normal) and preclinical, clinical ADRD (AD, FTD/ALS, DLB, PSP, CBD, VCID) data on MA Hispanic persons. Although our current brain samples are only 15% Hispanic, our fluid biobank has over 70% Hispanics and our focused attention on recruitment should increase the proportion of Hispanic brains to over 50% over the next 5 years. A 24/7 no-cost, autopsy service, post-mortem MRI, ante-mortem imaging/clinical assessments, family interviews, medical records increase the value of tissue obtained and shared with NACC. Interpreting ethnoracial pathological heterogeneity necessitates consideration of genetic and molecular variation, hence STAC has undertaken routine WES on the 56 brains donated to date (a 400% increase since our original submission) and proposes to undertake clinical genetic testing (with genetic counseling) in families of registered donors (Clinical and Genetics/Multiomics Cores), WGS on donated brain tissue and routinely preserves frozen brain tissue for additional omic (methylation, transcriptomics, ATAC-Seq, proteomics, metabolomics) studies. The NPC employs state-of-the-art genetic and “omics” approaches to aid in the interpretation of ADRD pathologies and identification of novel disease modifiers. The NPC undertakes routine digital scanning of all slides, and spatial neuropathology. The aims of the NPC are: accessioning high-quality central nervous system autopsy biospecimens, including brain, spinal cord, skin and cerebrospinal fluid (Aim 1); conducting data driven neuropathological evaluations of this material (Aim 2); maintaining these resources in a dynamic biorepository for use by a range of investigators (Aim 3); leading translational neuropathology research of multi-etiology dementia, including those of degenerative, cerebrovascular, and traumatic origins (Aim 4); and educating the local scientific/trainee (REC) and lay public communities on the importance of neuropathology and neurodegeneration research (Aim 5). The Neuropathology Core will accomplish these aims through collaborative relationships with other STAC Cores and external investigators, including colleagues at other Alzheimer’s Disease Centers.

了解异质性和交叉性神经退行性疾病的复杂性需要 中枢神经系统的综合定性和定量评估。 神经病理学核心 (NPC) 是南德克萨斯阿尔茨海默病中心 (STAC) 的关键组成部分，由其共同领导。 Kevin Bieniek 博士和 Jamie Walker 医学博士都接受过专门培训，旨在建立和领导一个新的 脑库，该核心全面表征大脑和脊髓，确认临床诊断， 研究目的，并向家庭提供诊断和建议。 阐明和干预阿尔茨海默病发病机制的未来进展 相关痴呆症 (ADRD) 需要对不同种族的尸检队列进行研究 STAC NPC 服务。 德克萨斯州南部地区有大量墨西哥裔美国西班牙裔人口，这将产生规范。 MA 的（认知正常）和临床前、临床 ADRD（AD、FTD/ALS、DLB、PSP、CBD、VCID）数据 虽然我们目前的大脑样本中只有 15% 是西班牙裔，但我们的液体生物库中有超过 70% 的西班牙裔。 西班牙裔和我们对招聘的关注应该将西班牙裔大脑的比例增加到超过 未来 5 年 50% 全天候（24/7）免费尸检服务、尸检 MRI、尸检成像/临床。 评估、家庭访谈、医疗记录增加了获得并与 NACC 共享的组织的价值。 解释民族病理异质性需要考虑遗传和分子因素 变异，因此 STAC 对迄今为止捐赠的 56 颗大脑进行了常规 WES（自此增加了 400%） 我们最初提交的材料）并提议在家庭中进行临床基因检测（并提供遗传咨询） 注册捐赠者的数量（临床和遗传学/多组学核心）、捐赠脑组织和常规的全基因组测序 保存冷冻脑组织用于其他组学（甲基化、转录组学、ATAC-Seq、蛋白质组学、 NPC 采用最先进的遗传和“组学”方法来帮助进行研究。 ADRD 病理学的解释和新疾病修饰因素的识别 NPC 进行常规工作。 所有载玻片的数字扫描和空间神经病理学。 NPC 的目标是： 加入高质量的中枢神经系统尸检生物标本， 包括大脑、脊髓、皮肤和脑脊液（目标 1）；进行数据驱动的神经病理学； 对该材料的评估（目标 2）；将这些资源保存在动态生物存储库中以供一定范围使用 研究人员数量（目标 3）；领先的多病因痴呆的转化神经病理学研究，包括 退行性、脑血管和创伤性起源的疾病（目标 4）并对当地科学家/实习生进行教育； (REC) 并向公众社区宣传神经病理学和神经变性研究的重要性 (Aim 5). 神经病理学核心将通过与其他 STAC 的合作关系来实现这些目标。 核心人员和外部研究人员，包括其他阿尔茨海默病中心的同事。