Neuropathology Core

The Neuropathology Core (NPC) fulfills several important roles within the University of Pittsburgh ADRC (PITT-ADRC). Postmortem neuropathological confirmation of the clinical diagnosis of Alzheimer’s disease (AD) and related disorders and the assessment of co-existing neurodegenerative and vascular disease processes is essential to promote progress in diagnosis, treatment and prevention of AD. Since its inception, the NPC has collected and characterized 868 brains from PITT-ADRC subjects at various disease stages. This resource has been extensively utilized for teaching purposes and for research studies by local and national investigators to develop amyloid PET imaging agents and correlate in vivo amyloid imaging results with postmortem findings, improve our understanding of genetic factors contributing to AD risk and advance our knowledge regarding the neurobiology of psychiatric comorbidities and neuroinflammatory processes. Our proposed approach to fulfill the diagnostic, tissue banking, research and educational roles of the NPC is outlined in five specific aims: 1) The NPC will continue to maintain and expand a well-catalogued bank of brain tissue samples and fibroblasts of ADRC participants and subjects from affiliated cohorts. A special emphasis will be placed on harvesting brains from subjects with premortem PiB and tau PET imaging studies and perform post-mortem 7T MRI on a select group of participants. 2) All banked cases undergo detailed diagnostic evaluation using the latest consensus criteria and detailed characterization of comorbid and aging-related pathologies. Results will be shared with ADRC clinical staff, families and uploaded to local and national databases (NACC). 3) The NPC will develop, implement and refine novel methods for postmortem tissue characterization such as postmortem MR imaging and digital image analysis algorithms for radiological-to- pathological alignments, quantification of pathology burden and creation of pathology endophenotypes. 4) The NPC will participate in local and national research efforts by providing brain bank tissue materials and neuropathology data from diagnostic evaluations. The NPC will closely collaborate with other PITT-ADRC cores and projects in joint research studies and will engage in NPC-driven research projects. 5) In collaboration with the Research Education Component, the NPC will leverage brain bank materials and expertise to educate neuropathology fellows, residents, medical students and investigators about the neuropathologic features of neurodegenerative diseases. Through these aims, the NPC will provide precise diagnostic classifications of PITT-ADRC research participants, enable studies of phenotype variations and broadly support efforts to improve our understanding of the underlying disease processes. Neuropathology Core Abstract: