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
- Timeline
- 2020–2025
- Status
- In Progress
Accomplishments/Implementation Activities
Funding Initiatives
- RFA-NS-20-005: Mechanistic Basis of TDP-43-dependent Pathobiology in Common Dementias (R01)
- RFA-NS-21-003 –Center without Walls for Mechanisms of Neurodegeneration in Frontotemporal Dementia (FTD)