U01NS137484

Neuroimaging and clinical endpoints with high-dimensional analysis of pathological endophenotypes in TBI (NEW-HOPE-TBI) - Project summary/abstract

Alzheimer’s disease and related dementias (ADRDs) are highly prevalent, devastating to patients and their loved ones, and encompass a diversity of etiologies and pathologies.

Traumatic brain injury (TBI) and repetitive head impacts (RHI) can contribute to the initiation and/or acceleration of ADRDs, including chronic traumatic encephalopathy (CTE), but critical gaps in knowledge prevent the development of effective diagnostic strategies and therapeutic interventions.

Most importantly, mechanisms through which diverse patterns of head trauma increase risk for AD/ADRD/CTE are not known, nor is it clear how multiple pathological processes interact to influence symptom manifestation and disease progression.

These knowledge gaps must be addressed to enable in vivo diagnosis and disease-modifying therapeutics in our lifetime - the highest-priority recommendation for post-TBI AD/ADRD from the 2022 ADRD Summit.

To address these critical issues, we propose NEW-HOPE-TBI, a unique and powerful cohort and open-access biospecimen, imaging, and data resource to enable and enhance research to better understand connections between macroscopic (neuroimaging) and microscopic (neuropathology) features of posttraumatic AD/ADRD/CTE.

To accomplish this, we propose to expand our existing nationwide network of well-characterized brain donors from diverse cohorts with heterogeneous TBI exposures and/or AD/ADRD (Aim 1), broadly characterize co-pathology burden about head trauma (HT) exposure patterns (Aim 2), identify quantitative neuropathology and imaging signatures of cognitive and behavioral decline in chronic TBI and post-traumatic neurodegeneration (Aim 3), and deeply phenotype meso- to micro-scale vascular pathology in TBI (Aim 4).

Through this work, we will build a unique open-access biospecimen and data biorepository that includes digital pathology and imaging data linked to accessible brain tissues and biofluids, and critical metadata including TBI exposure history, cognitive and behavioral health metrics, and social determinants of health, from well-characterized research donors (Aim 5).

We have assembled a world-class team of scientists, clinicians, neuroimagers, neuropathologists, and biostatisticians to fulfill the goals of this proposal, including Dr. Tim Brown, a bioethics expert who is committed to advising NEW-HOPE-TBI concerning diversity, equity, and inclusion in our research team and cohort.

Finally, to promote AD and ADRD neuropathology research far into the future, we place great emphasis on the career development and engagement of junior neuropathologists and fellows who represent the next generation of post-traumatic neurodegenerative neuropathology researchers.

The proposed work is made possible by leveraging clinical TBI and AD/ADRD studies, network-based autopsy with ex vivo MRI, postmortem data that far exceed the NIH CDES, a world-class team of senior, mid-level, and early-stage investigators, and a unique focus on neuroethics to enhance diversity in neuropathology research.

No other team in the world can lead the science and data sharing proposed herein.

University Of Washington

(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]

Seattle, Washington 981951016 United States

Single Zip Code

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 140% from $1,756,811 to $4,213,033.