R01NS139383

Risk and resilience, clinical presentation, and biomarker profiles of chronic traumatic encephalopathy and related dementias: The Diagnose CTE Research Project II - Chronic Traumatic Encephalopathy (CTE) is a neurodegenerative disease diagnosed postmortem in people exposed to repetitive head impacts (RHI) from football and other contact sports.

NINDS consensus research diagnostic criteria for the clinical syndrome of CTE, known as Traumatic Encephalopathy Syndrome (TES), were published in 2021.

However, we cannot diagnose CTE in life due to the following knowledge gaps: 1) TES criteria do not include biomarkers, limiting disease specificity; (2) longitudinal studies are lacking; (3) biomarkers and clinical features that distinguish CTE from other AD/ADRDs are unknown; and (4) risk/resilience factors of TES are unclear, particularly social determinants of health (SDOH).

In 2015, we were awarded a NINDS funded 7-year U01 known as the Diagnose CTE Research Project (Diagnose), designed in part to develop biomarkers of CTE.

It enrolled 180 former football players (120 professional, 60 college) and 60 non-RHI controls, all males ages 45-74.

Baseline clinical exams, MRI, TAU (flortaucipir) and amyloid PET, and blood draws were completed in 2020.

Four-year remote follow-ups, including in-home blood draws, were finished in Nov. 2023.

We had a 90% retention rate.

The goals of this R01 are to retain and grow Diagnose and examine the clinical and biomarker course and profiles of TES (Aim 1); investigate risk/resilience factors of TES (Aim 2); and compare biomarkers of amyloid (Aβ), P-tau, neurodegeneration, neuroinflammation, and white matter injury between TES and AD syndromes (Aims 3-4).

Our hypotheses are that TES has unique clinical and biomarker profiles, and RHI and non-RHI risk factors influence the development of TES.

There will be 3 groups: (1) Retention, 150 former football players and 50 controls retained from Diagnose; (2) Expansion, we will grow Diagnose by newly recruiting 75 former college and professional football players and 25 controls; (3) AD, 50 Aβ+ participants with cognitive impairment.

In total, we will study 225 former football players, 75 controls, and 50 AD.

Groups will be similar in age (50+), sex (males), and race (40% Black).

Participants will complete a single visit, including clinical exams, SDOH measures, MRI, blood draw, and TAU PET, at 1 of 5 P30 AD research centers: BU, UCSF, Arizona, 1Florida, or South Texas.

Retention cohort will have flortaucipir PET to study its longitudinal value.

Expansion cohort will have MK-6240 PET to build on our R21.

A subset of retention (N=20) will have flortaucipir and MK-6240 for tracer comparison.

Blood will be analyzed for 6 P-tau epitopes, Aβ40/42, neuroinflammation, and white matter injury.

Retention cohort will have legacy data for longitudinal study of outcomes (2-3 timepoints over 6-8 years).

Expansion will contribute to pooled cross-sectional analyses.

Diagnose participants were asked for brain donation; 8 have donated.

This R01 will permit continued brain donation and clinical-pathological validation studies.

This R01 will retain and grow a unique, deeply phenotyped, longitudinal cohort of people at risk for CTE.

Results will help refine the TES criteria and differentiate it from other AD/ADRDs.

This R01 will provide insight into the detection, diagnosis, and prognosis for people living with CTE, paving the way for treatment trials.

Trustees Of Boston University

(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]

Boston, Massachusetts 021182642 United States

Single Zip Code

Research on Current Topics in Alzheimer's Disease and Its Related Dementias (R01 Clinical Trial Optional) (PAR-22-093)

Amendment Since initial award the total obligations have increased 92% from $3,289,394 to $6,308,426.