The overarching goals of the Brain Banking Core (BBC) are to conduct and foster research on RHI and TBI and to determine associations with AD, ADRD, CTE, and other neurodegenerative pathology as well as clinical outcomes. The BBC will include 8 brain bank cohorts, 6 from Boston University School of Medicine (BUSM) and the VA Boston Healthcare System: the BU Alzheimer Disease Center (BUADC), Framingham Heart Study (FHS), VA Post-Traumatic Stress Disorder (PTSD), VA amyotrophic lateral sclerosis (ALS), Chronic Effects of Neurotrauma (CENC) and VA-BU-CLF (UNITE) and 2 from the Icahn School of Medicine at Mount Sinai (ISMMS) to systematically evaluate the precise neuropathology of RHI and TBI-related neurodegeneration. These combined brain banks contain over 2500 cases, and include the largest neuropathologically confirmed autopsy cohort of CTE subjects (n= 361) in the world. In addition, the LETBI, CENC, ALS, and UNITE brain banks hold at least 50 cases of remote, moderately-severe TBI with a chronic cavitary lesion (cTBI).
The specific aims of the BBC consist of fundamental Core functions, namely to perform state-of-the-art diagnostic neuropathology, optimally store and distribute CNS tissue and other biospecimens, and provide neuropathological data for Projects 1-3 and to the Federal Interagency Traumatic Brain Injury Research (FITBIR) for the general scientific community. All neuropathological protocols will be aligned with those proposed by the NINDS Neuropathological CTE Consensus Conference for biospecimen collection, blocking, staining and storage, which the PI led and helped establish. In addition, a digital library of the pathology slides will be generated for each participant and made publicly available. Finally, the BBC will work to develop novel methods for the assessment of RHI and cTBI-related injury to include axonal and white matter degeneration, gliosis, and inflammation.
The specific aims also build upon the significant innovations of the PI and investigators with regard to RHI, cTBI, and CTE and focus on determining the pathological and clinical associations following brain impacts and injury. To accomplish these aims, the BBC will work in close collaboration with the Administration and Data Cores and Projects 1-3, as well as the associated ISMMS Alzheimer's Disease and Research Center Brain Bank and the BUADC. Overall, the BBC will provide a harmonized neuropathological workup and assessment in order to facilitate the storage and distribution of biospecimens, comprehensive diagnoses, digital library creation, and the development of novel quantitative neuropathological measures in order to best capture the chronic sequalae of RHI and TBI. Specimens and data collected by the BBC will be linked to RHI and TBI history determined in Project 1, harmonized clinical outcomes assessed in Project 2, and additional pathological and inflammatory measures determined in Project 3. The harmonized data will be used extensively across Projects 1-3 and made widely available for outside investigators.
