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Milestone 2.U

AD Related Dementias – Specific

Determine underlying pathobiologic and molecular mechanisms of cellular TDP-43 displacement, post-translational modifications such as phosphorylation, and pathology in pre-symptomatic and manifest common dementias.

Success Criteria

  • Support at least one new initiative that fosters rigorous research focused on advancing knowledge on the systems, cellular and/or molecular mechanisms and consequences of TDP-43 proteinopathy in common dementias using in vivo models, cellular models and/or human biospecimens.

Summary of Key Accomplishments

TDP-43 is a protein that is found in all cells, is essential for life, and is known to aggregate in multiple neurodegenerative diseases, including some with dementia as a symptom. Genetic and biological links between TDP-43 and a dementia diagnosis have recently gained appreciation and emphasize the need to understand what is happening with TDP-43 during life and in early and late stages of dementia. The NIH initiative “Mechanistic Basis of TDP-43-dependent Pathobiology in Common Dementias” (RFA-NS-20-005) directly responds to this milestone and is supporting three new projects. One project used clinical and neuropathological data from community-based studies to trace people’s health over time and found that dementia-associated changes in TDP-43 were commonly seen both together with and without other dementia-related changes in the brain.

This information is current as of July 2022.

Research Implementation Area
AD Related Dementias - Specific
In Progress

Accomplishments/Implementation Activities

Funding Initiatives

Relevant Recommendations

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