South Texas Alzheimer's Disease Center Neuropathology Core

了解异质性和交叉性神经退行性疾病的复杂性需要 对中枢神经系统进行全面的定性和定量评估。因此， 神经病理学核心(NPC)是南得克萨斯州阿尔茨海默病中心(STAC)的关键组成部分。由联合领导 Kevin Bieniek博士和Jamie Walker博士，他们都接受过专门的培训，以建立和领导一个新的 Brain Bank，这一核心全面表征了大脑和脊髓，以确认临床诊断， 研究的目的，并为家庭提供诊断和建议。 阿尔茨海默病发病机制的阐明和干预的未来进展 相关痴呆(ADRD)需要对不同的人种尸检队列进行研究。国家发改委全国人大服务 南得克萨斯州地区的一大批墨西哥裔拉美裔美国人。它将产生规范性 (认知正常)和临床前、临床ADRD(AD、FTD/ALS、DLB、PSP、CBD、VCID)关于MA的数据 西班牙裔人。尽管我们目前的大脑样本只有15%是西班牙裔，但我们的液体生物库有超过70%的 拉美裔和我们对招聘的关注应该会增加拉美裔大脑的比例 在接下来的5年里增加50%。24/7全天候免费尸检服务、尸检MRI、尸检成像/临床 评估、家庭访谈、医疗记录增加了获得的组织的价值，并与NACC分享。 解释民族病理异质性需要考虑遗传和分子因素 因此，STAC对迄今捐赠的56个大脑进行了常规的WES(自 我们的原始意见书)，并建议在家庭中进行临床基因测试(带有遗传咨询) 注册供者(临床和遗传学/多重组学核心)，WGS对捐赠的脑组织和常规 保存冷冻脑组织以进行额外的基因组学(甲基化、转录组学、ATAC-Seq、蛋白质组学、 代谢组学)研究。全国人大使用最先进的遗传和“组学”方法来帮助 ADRD病理的解释和新的疾病修饰物的鉴定。全国人大进行例行公事 所有切片的数字扫描，以及空间神经病理学。 NPC的目标是：获得高质量的中枢神经系统尸检生物标本， 包括脑、脊髓、皮肤和脑脊液(目标1)；进行数据驱动的神经病理学 对这种材料的评价(目标2)；将这些资源保存在一个动态生物储存库中，供一系列动物使用 研究人员(目标3)；领导多病因痴呆的翻译神经病理学研究，包括 退行性、脑血管和创伤性疾病(目标4)；以及教育当地的科学家/受训人员 (Rec)和向公众社区宣传神经病理学和神经退行性变研究的重要性(Aim 5)。神经病理核心将通过与其他STAC的合作关系来实现这些目标 核心和外部调查人员，包括其他阿尔茨海默病中心的同事。

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.