Official websites use .gov

A .gov website belongs to an official government organization in the United States.

Secure .gov websites use HTTPS

A lock ( 🔒 ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.

Need Help

The Late Effects of TBI (LETBI) Study: Injury Patterns and Biological Markers of Post-Traumatic Neurodegeneration

Award Number: RF1NS115268
ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/15/2019
PERIOD OF PERFORMANCE END DATE: 01/31/2029

Group Awards By:

View Award Description

The Late Effects of TBI (LETBI) Study: Injury Patterns and Biological Markers of Post-Traumatic Neurodegeneration - Project Summary/Abstract Traumatic brain injury (TBI) is a recognized risk factor for Alzheimer’s disease (AD) and related dementias (ADRDs), and factors such as number of lifetime TBIs, TBI severity, and patterns of injury including exposure to repetitive head impacts (RHI) have important implications for long-term clinical and pathological sequelae. The clinical phenotypes and pathological processes through which a TBI initiates and/or accelerates AD/ADRD pathogenesis (i.e., post-traumatic neurodegeneration (PTND)) remain unknown. We will address this gap in the proposed competitive renewal by longitudinally following a large, well-characterized cohort of over 500 individuals living with chronic TBI: the Late Effects of TBI (LETBI) study. LETBI participants have completed cognitive and neurobehavioral evaluations, blood draws, neuroimaging, and have made known their wishes for brain donation. With unparalleled multimodal longitudinal data, we will identify in-vivo clinical and biological markers of PTND to inform early diagnosis, prognosis, disease monitoring, and future mechanistic studies. We will address the overarching hypothesis that distinct patterns of lifetime head trauma contribute to clinical decline that can be predicted during life by noninvasive blood biomarkers and reflected in neuroimaging indices of neurovascular, neuroinflammatory, and neurodegenerative disease. We will validate in-vivo biomarkers in the LETBI autopsy cohort by quantifying polypathology burden in decedents with distinct injury patterns. Identifying in-vivo biological markers of PTND is of high priority given the population prevalence of TBI and the urgent need to identify disease-modifying therapeutics for AD/ADRD. Our work is organized around 3 Specific Aims: 1. To test the hypothesis that greater number of TBIs, more severe TBI, and RHI exposures are associated with clinical decline by quantifying the contributions of distinct patterns of lifetime TBI exposure to cognitive, neurobehavioral, and motor function over time. 2. To test the hypothesis that a panel of clinically accessible blood biomarkers can predict a) multi-domain clinical decline, and b) are related to progression in neuroimaging indices of neurovascular disease, neuroinflammation, and neurodegeneration that are detectable on MRI. 3. In the LETBI autopsy cohort, we will determine the pathological substrates of distinct TBI exposure patterns by testing the hypotheses that a) vascular, inflammatory, and neurodegenerative pathology burden differs across head trauma exposure patterns; and b) quantitative polypathology burden is highest in pericontusional regions. Our multidisciplinary team is uniquely positioned to advance understanding of the late effects of TBI. We will apply a novel biomarker discovery platform, innovative neuroimaging techniques, and multimodal autopsy methods to a large heterogeneous cohort of TBI survivors to accelerate scientific knowledge of the complex polypathology of TBI and PTND for improved diagnostics and care.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $3,354,854 )
2026	2026	ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI	1 GUSTAVE L LEVY PL	NEW YORK	NY	10029	NEW YORK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	2	3/12/2026	COMPETING CONTINUATION	$0
2026	2026	ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI	1 GUSTAVE L LEVY PL	NEW YORK	NY	10029	NEW YORK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	2	2/10/2026	COMPETING CONTINUATION	$3,354,854
														Subtotal = $3,354,854

Issue Date FY: 2024 ( Subtotal = $0 )
2024	2019	ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI	1 GUSTAVE L LEVY PL	NEW YORK	NY	10029	NEW YORK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	1/31/2024	NEW	$0
2024	2019	ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI	1 GUSTAVE L LEVY PL	NEW YORK	NY	10029	NEW YORK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	1	2/21/2024	NEW	$0
														Subtotal = $0

Issue Date FY: 2020 ( Subtotal = $0 )
2020	2019	ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI	ONE GUSTAVE L LEVY PL	NEW YORK	NY	10029	NEW YORK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	1/8/2020	NEW	$0
														Subtotal = $0

Issue Date FY: 2019 ( Subtotal = $6,907,906 )
2019	2019	ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI	ONE GUSTAVE L LEVY PL	NEW YORK	NY	10029	NEW YORK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	9/14/2019	NEW	$6,907,906
														Subtotal = $6,907,906

Grand Total All Awards = $10,262,760

Top

All Categories

About

Search

Reports

Data Submission

Award Information

The Late Effects of TBI (LETBI) Study: Injury Patterns and Biological Markers of Post-Traumatic Neurodegeneration

Award Number: RF1NS115268

ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 09/15/2019

PERIOD OF PERFORMANCE END DATE: 01/31/2029

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer