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AD-Related Dementias Focus
Basic and translational research to elucidate the mechanistic pathways, development, and progression of post-TBI AD/ADRD neuro-pathologies to better understand clinical symptom expression.
2029 RFA-NS-19-026: Clinical and Biological Measures of TBI-related dementia including Chronic Traumatic Encephalopathy (CTE) (R01) RFA-NS-19-030: Neuropathological Assessment of TBI-related Neurodegeneration and Neurocognitive Decline - Center Without Walls (NATBI CWOW) (U54) RFA-NS-20-004: Molecular Mechanisms of Blood-Brain Barrier Function and Dysfunction in Alzheimer's disease and Alzheimer's related dementias PAR-22-024: Clinical and Biological Measures of TBI-related Dementia Including Chronic Traumatic Encephalopathy (R01 Clinical Trial Not Allowed) 2.W In Progress Promote basic and clinical research examining the development and progression of TBI AD/ADRD neuropathologies and associated clinical symptoms. DN 2019 ADRD Summit: Emerging Scientific Topics, Focus Area 2: TBI and AD/ADRD Risk, Milestone 7 2022 ADRD Summit: Multiple Etiology Dementias (MED) Special Topic: Post-TBI AD/ADRD Milestone 4, Priority 4 News: Microbleeds may worsen outcome after head injury News: Researchers discover hidden differences between pathology of CTE and Alzheimer's disease Research on Disease Mechanisms Clinical and Biological Measures of TBI-related dementia including Chronic Traumatic Encephalopathy (CTE) (R01) Neuropathological Assessment of TBI-related Neurodegeneration and Neurocognitive Decline - Center Without Walls (NATBI CWOW) (U54) Select projects funded in FY21 Select projects funded in FY22
- To facilitate translational research, develop at least one new TBI animal model that has sustained cognitive decline and progressive changes in the brain associated with AD/ADRD cognitive impairment and dementia outcomes in humans following TBI.
- At least two new projects to identify molecular mechanisms resulting from TBI that lead to cognitive impairment and dementia.
- Support one project to connect preclinical data and clinical data to identify potential drug targets.
Summary of Key Accomplishments
Epidemiological data suggest that a history of TBI is a significant risk factor for AD/ADRD and that the relative risk may be mediated by injury severity and frequency with increased severity and multiple insults resulting in higher risk. Ongoing NIH-funded studies are currently characterizing the neuropathological features of chronic TBI associated with neurodegeneration and neurocognitive decline. For example, a recent study demonstrated that long term TBI-related brain changes appeared to be subtle and involved non-traditional pathways of neurotoxicity and neurodegeneration.
Another NIH-funded study revealed that brain tissue from individuals who had suffered repetitive head injuries exhibited brain pathologies like those seen in AD/ADRD brains, including markers of immune reaction and tau pathology. Collectively, these findings inform future research on TBI-related dementia including CTE, and two NIH-funded studies are currently developing neuroimaging resources and tools for multi-scale and multi-modality assessment of TBI-related dementia and VCID.
NIH-funded researchers are also working to better understand how the complex interaction between the brain and the structure and function of the gut microbiome impacts cognitive outcomes following TBI. For example, one group of NIH-funded scientists are investigating mechanisms linking alterations in the aged gut microbial community to subsequent AD/ADRD following TBI and testing the hypothesis that restoration of a youthful gut microbiome before or after TBI will improve cognitive outcomes. This builds on a recent study showing that mice fed a diet including probiotics experienced less neuroinflammation and fewer behavioral deficits following TBI.
In FY2024, NIH released a funding opportunity to support and accelerate the development, characterization, and validation of mammalian TBI models that display progressive clinical and pathological characteristics of ADRD following TBI, including CTE.
The key accomplishments summary is current as of July 2024.