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

基本信息

批准号：
10472674
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
项目类别：
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/10472674
关键词：
ATAC-seq Address Alzheimer&apos s Disease Alzheimer&apos s disease related dementia Amyloid beta-Protein Archives Area Attention Autopsy Bar Codes Basic Science Behavior Biological Markers Blood Vessels Brain Brain region Cerebrospinal Fluid Cities Clinic Clinical Clinical assessments Cognitive Communities Comprehensive Health Care DNA DNA analysis Data Data Set Databases Dementia Diagnosis Diagnostic Disease Dissection Doctor of Philosophy Epigenetic Process Ethnic group Etiology Evaluation Family Fostering Foundations 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 Neuraxis 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 Walkers aging brain alpha synuclein biobank brain tissue cerebrovascular clinical diagnosis cohort cost data management digital digital pathology education research endophenotype ethnic diversity 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 chronic conditions multiple omics nano-string neurofilament neuropathology normal aging novel outreach population based pre-clinical precision medicine preservation protein TDP-43 protein biomarkers racial and ethnic racial diversity recruit repository statistics tau Proteins trait transcriptomics

项目摘要

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.

了解异质和相交神经退行性疾病的复杂性需要中枢神经系统的全面定性和定量评估。因此，神经病理学核心（NPC）是南德克萨斯州阿尔茨海默氏症中心（STAC）的关键组成部分。共同领导凯文·比尼克（Kevin Bieniek）博士和医学博士Jamie Walker均受过训练，专门为建立和领导新的培训大脑库，该核心全面表征了大脑和脊髓确认临床诊断，因为研究目的，并向家庭提供诊断和建议。未来阐明和干预阿尔茨海默氏病的发病机理的未来进步相关的痴呆症（ADRD）需要研究潜水员种族尸检队列。 STAC NPC服务南德克萨斯州一个墨西哥裔美国人西班牙裔人口。它会产生正常（认知正常）和临床前，临床ADRD（AD，FTD/ALS，DLB，PSP，CBD，VCID）西班牙裔人。尽管我们目前的大脑样本只有15％的西班牙裔，但我们的液体生物库的占70％以上西班牙裔和我们对招聘的关注应该增加西班牙裔大脑的比例在未来5年内50％。 24/7无术，尸检服务，验尸MRI，前验证成像/临床评估，家庭访谈，病历增加了与NACC获得和共享的组织的价值。解释民族种族的病理异质性，需要考虑遗传和分子因此，变异，因此，迄今为止，Stac对捐赠的56个大脑进行了例行WES（自从以来增加了400％我们最初的提交）和家庭对家庭进行临床基因检测的建议注册供体（临床和遗传学/多构核），捐赠的脑组织WGS和常规保存冷冻的脑组织，以进行其他OMIC（甲基化，转录组学，ATAC-SEQ，蛋白质组学，代谢组学）研究。 NPC员工最先进的遗传和“ OMIC”方法来帮助 ADRD病理学的解释和新型疾病修饰剂的鉴定。 NPC进行例行所有幻灯片和空间神经病理学的数字扫描。 NPC的目的是：加入高质量的中枢神经系统尸检生物测量，包括大脑，脊髓，皮肤和脑脊液（AIM 1）；进行数据驱动神经病理学评估该材料（AIM 2）；将这些资源维护在动态的生物设备中，以供范围调查人员（目标3）；多属性痴呆的领先的转化神经病理学研究，包括退化性，脑血管和创伤性的那些（AIM 4）；并教育当地的科学/学员（REC）和公共社区关于神经病理学和神经退行性研究的重要性（AIM） 5）。神经病理学核心将通过与其他Stac的协作关系来实现这些目标核心和外部研究人员，包括其他阿尔茨海默氏病中心的同事。