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。所以 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。共同领导 凯文Bieniek博士和杰米步行者，医学博士，都受过专门的培训，建立和领导一个新的 Brain Bank，这一核心全面表征大脑和脊髓，确认临床诊断， 研究目的，并为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， 相关性痴呆（ADRD）需要对不同民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。它将产生规范的 MA的临床前、临床ADRD（AD、FTD/ALS、DLB、PSP、CBD、VCID）数据 西班牙人。虽然我们目前的大脑样本只有15%是西班牙裔，但我们的流体生物库有超过70%的 西班牙裔和我们对招聘的关注应该会增加西班牙裔大脑的比例， 在未来五年内达到50%。24/7免费，尸检服务，死后MRI，生前成像/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。 解释民族病理学异质性需要考虑遗传和分子生物学因素。 变异，因此STAC对迄今为止捐赠的56个大脑进行了常规WES（自2010年以来增加了400%）。 我们最初提交的文件），并建议在家庭中进行临床基因检测（遗传咨询） 注册供体（临床和遗传学/多组学核心），捐赠脑组织的WGS和常规 保存冷冻的脑组织用于额外的组学（甲基化，转录组学，ATAC-Seq，蛋白质组学， 代谢组学）研究。NPC采用最先进的遗传学和“组学”方法来帮助 ADRD病理学的解释和新疾病修饰物的鉴定。全国人大承担日常工作 所有切片的数字扫描和空间神经病理学。 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 评估这种材料（目标2）;将这些资源保存在动态生物储存库中，供一系列生物使用 的研究者（目标3）;领先的多病因痴呆的转化神经病理学研究，包括 退行性疾病、脑血管疾病和创伤性疾病（目标4）;以及教育当地的科学家/受训者 (REC)并向公众宣传神经病理学和神经变性研究的重要性（目的 5）。神经病理学核心将通过与其他STAC的合作关系实现这些目标 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.