U01NS137500

Transdisciplinary Research Accelerating Neuropathology Studies and Facilitating Open Research Methods in TBI (TRANSFORM-TBI) - Traumatic Brain Injury (TBI) is recognized as a modifiable risk factor for neurodegenerative diseases, including Alzheimer’s Disease and Alzheimer’s Disease-Related Dementias (AD/ADRD).

As such, there has been an explosion of interest in the link between TBI and the development of late neurodegenerative pathologies, particularly Chronic Traumatic Encephalopathy Neuropathologic Change (CTE-NC). However, the intense focus on CTE-NC has come at the expense of investigation of the broader spectrum of pathologies found after all forms of TBI.

Accordingly, we have adopted the conceptual framework, “TBI-Related Neurodegeneration” (TREND), of which CTE-NC is just one form. Notably, studies in TBI offer a unique opportunity to discover mechanisms of neurodegeneration, since the initiating event or events – ‘time zero’- are known, thereby permitting the temporal examination of the progression of pathology.

Indeed, for over two decades, our group has led the meticulous description of multiple neurodegenerative pathologies in individuals with a history of repetitive mild TBI or single severe TBI. In 2019, we established a NINDS-supported U54 Center Without Walls, CONNECT-TBI, which has become internationally recognized for its success in coordinating prospective tissue banking in TBI, across all injury severities and exposures.

To date, CONNECT-TBI has gathered unrivaled clinical datasets and tissue archives, including over 1000 prospectively collected cases across participating centers. Here, as we enter our final year of U54 support for CONNECT-TBI, we propose the next phase initiative; “Transdisciplinary Research Accelerating Neuropathology Studies and Facilitating Open Research Methods in TBI” (TRANSFORM-TBI).

This initiative seeks to continue and expand the CONNECT-TBI archive, which we will leverage to explore relationships between TREND, pathologies of AD/ADRD, and their contribution to late clinical outcomes. We also propose to democratize access to this resource to accelerate the discovery of TREND pathologies and their significance. In so doing, we have established an expert, multidisciplinary team of 26 investigators across 12 sites who will identify associations between the extent and type of neuropathological changes emerging following exposure to TBI of all severities (repetitive mild to single severe) and exposures (including sports, military, intimate partner violence).

These neuropathological findings will then be compared with extensive clinical datasets to assess potential clinical correlations. Specifically, we aim to, 1) explore the pathologic heterogeneity of TREND, including the prevalence and spectrum of AD/ADRD pathologies in late survival from TBI, 2) characterize TREND-associated glial pathology and contrast it with the glial pathology of wider AD/ADRD, 3) examine TREND associated clinical phenotypes and their distinction from those of aging and wider, non-TBI related AD/ADRD, and 4) establish a digital slide archive and open research environment (Digital Scope) to support innovative, investigator-led studies across the global research community.

Trustees Of The University Of Pennsylvania

(1) TO SUPPORT EXTRAMURAL RESEARCH FUNDED BY THE NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE (NINDS) INCLUDING: BASIC RESEARCH THAT EXPLORES THE FUNDAMENTAL STRUCTURE AND FUNCTION OF THE BRAIN AND THE NERVOUS SYSTEM, RESEARCH TO UNDERSTAND THE CAUSES AND ORIGINS OF PATHOLOGICAL CONDITIONS OF THE NERVOUS SYSTEM WITH THE GOAL OF PREVENTING THESE DISORDERS, RESEARCH ON THE NATURAL COURSE OF NEUROLOGICAL DISORDERS, IMPROVED METHODS OF DISEASE PREVENTION, NEW METHODS OF DIAGNOSIS AND TREATMENT, DRUG DEVELOPMENT, DEVELOPMENT OF NEURAL DEVICES, CLINICAL TRIALS, AND RESEARCH TRAINING IN BASIC, TRANSLATIONAL AND CLINICAL NEUROSCIENCE. THE INSTITUTE IS THE LARGEST FUNDER OF BASIC NEUROSCIENCE IN THE US AND SUPPORTS RESEARCH ON TOPICS INCLUDING BUT NOT LIMITED TO: DEVELOPMENT OF THE NERVOUS SYSTEM, INCLUDING NEUROGENESIS AND PROGENITOR CELL BIOLOGY, SIGNAL TRANSDUCTION IN DEVELOPMENT AND PLASTICITY, AND PROGRAMMED CELL DEATH, SYNAPSE FORMATION, FUNCTION, AND PLASTICITY, LEARNING AND MEMORY, CHANNELS, TRANSPORTERS, AND PUMPS, CIRCUIT FORMATION AND MODULATION, BEHAVIORAL AND COGNITIVE NEUROSCIENCE, SENSORIMOTOR LEARNING, INTEGRATION AND EXECUTIVE FUNCTION, NEUROENDOCRINE SYSTEMS, SLEEP AND CIRCADIAN RHYTHMS, AND SENSORY AND MOTOR SYSTEMS. IN ADDITION, THE INSTITUTE SUPPORTS BASIC, TRANSLATIONAL AND CLINICAL STUDIES ON A NUMBER OF DISORDERS OF THE NERVOUS SYSTEM INCLUDING (BUT NOT LIMITED TO): STROKE, TRAUMATIC INJURY TO THE BRAIN, SPINAL CORD AND PERIPHERAL NERVOUS SYSTEM, NEURODEGENERATIVE DISORDERS, MOVEMENT DISORDERS, BRAIN TUMORS, CONVULSIVE DISORDERS, INFECTIOUS DISORDERS OF THE BRAIN AND NERVOUS SYSTEM, IMMUNE DISORDERS OF THE BRAIN AND NERVOUS SYSTEM, INCLUDING MULTIPLE SCLEROSIS, DISORDERS RELATED TO SLEEP, AND PAIN. PROGRAMMATIC AREAS, WHICH ARE PRIMARILY SUPPORTED BY THE DIVISION OF NEUROSCIENCE, ARE ALSO SUPPORTED BY THE DIVISION OF EXTRAMURAL ACTIVITIES, THE DIVISION OF TRANSLATIONAL RESEARCH, THE DIVISION OF CLINICAL RESEARCH, THE OFFICE OF TRAINING AND WORKFORCE DEVELOPMENT, THE OFFICE OF PROGRAMS TO ENHANCE NEUROSCIENCE WORKFORCE DEVELOPMENT, AND THE OFFICE OF INTERNATIONAL ACTIVITIES. (2) TO EXPAND AND IMPROVE THE SMALL BUSINESS INNOVATION RESEARCH (SBIR) PROGRAM, TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, TO INCREASE SMALL BUSINESS PARTICIPATION IN FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION. TO UTILIZE THE SMALL BUSINESS TECHNOLOGY TRANSFER (STTR) PROGRAM, TO STIMULATE AND FOSTER SCIENTIFIC AND TECHNOLOGICAL INNOVATION THROUGH COOPERATIVE RESEARCH AND DEVELOPMENT CARRIED OUT BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO FOSTER TECHNOLOGY TRANSFER BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION.

93.866 - Aging Research

National Institute of Neurological Disorders and Stroke (NNDS) [HHS - NIH]

National Institute on Aging (NIA) [HHS - NIH]

Pennsylvania United States

State-Wide

Assessment of TBI-related ADRD Pathology Related to Cognitive Impairment and Dementia Outcomes (U01 - Clinical Trial Not Allowed) (RFA-NS-24-003)

Amendment Since initial award the total obligations have increased 94% from $2,032,044 to $3,951,871.