Neuropathology

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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.