Neuropathology

项目总结(见说明)： 核心B是一个神经病理和生物标记物核心(NP核心)，在UCSF FTD PPG中起着至关重要的作用。 近年来，FTLD神经病理学变得越来越令人兴奋和复杂，通过这种PPG完成的W/ORK取得了重大进展。在过去的两个周期里。核心B由宾夕法尼亚大学(宾夕法尼亚大学)的John Trojanowski博士领导。在此续订申请中，我们建议通过William Seeley博士领导的NP Core将核心B职能集中在加州大学旧金山分校，并增加新的 由宾夕法尼亚大学Trojanowski博士和Leslie Shaw博士领导的脑脊液(CSF)生物标记物成分。新的NP Core的目标是：(1)通过对通过Core A确定的患者和健康对照进行及时的尸检，获得用于NP表征和银行的CNS组织；(2)分析标本和记录NP 通过解剖一组标准的23个感兴趣区域进行常规组织学染色和系统的免疫组织化学表征进行诊断；(3)将NP的发现输入以研究为导向的综合数据库；(4)通过审查委员会的组织请求并将样本提供给合格的研究人员来储存和分发中枢神经系统组织；以及(5)存储和分析用于诊断的脑脊液 通过平均每年从45名临床诊断为FTD或AD的患者那里接收脑脊液样本，并对每个样本进行脑脊液总tau、磷酸tau和β-淀粉样蛋白水平的检测。这些核心功能将通过提供作为主要结果或分组变量的最终神经病理诊断来支持项目2(多模式成像)、项目3(情绪)和项目4(临床标准)的目标。此外，NP Core将有助于进一步开发一个独特的经过特殊处理的中枢神经系统组织(脑、脊髓和脑脊液)库，用于正在进行的和未来的FTLD分子、翻译、临床病理和生物标记物发现研究。

PROJECT SUMMARY (See instructions): Core B is a Neuropathology and Biomarker Core (NP Core) that plays a vital role in the UCSF FTD PPG. FTLD neuropathology has become increasingly exciting and complex in recent years, with major advances arising from w/ork accomplished through this PPG. During the past two cycles. Core B has been led by Dr. John Trojanowski at the University of Pennsylvania (PENN). In this renewal application, we propose to centralize Core B functions at UCSF through an NP Core led by Dr. William Seeley and to add a new cerebrospinal fluid (CSF) biomarker component led by Drs. Trojanowski and Leslie Shaw at PENN. The new NP Core aims to: (1) Obtain CNS tissue for NP characterization and banking by performing timely autopsies on patients and healthy controls ascertained through Core A; (2) Analyze specimens and document NP diagnoses by dissecting a standard set of 23 regions-of-interest for routine histological staining and systematic immunohistochemical characterization; (3) Enter NP findings into a comprehensive research oriented database; (4) Bank and distribute CNS tissues by reviewing tissue requests by committee and providing samples to qualified investigators for research; and (5) Store and analyze CSF for diagnostic biomarkers by receiving CSF samples from an average of 45 patients per year with FTD or AD clinical diagnoses and performing CSF total tau, phospho-tau and beta-amyloid levels on every sample. These core functions will support the aims of Projects 2 (Multi-modal imaging), 3 (Emotions), and 4 (Clinical criteria) by providing final neuropathological diagnoses that serve as primary outcomes or grouping variables. Moreover, the NP Core will help to futher develop a unique bank of specially handled CNS tissues (brain, spinal cord, and CSF) for ongoing and future FTLD molecular, translational, clinicopathological, and biomarker discovery research.