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AD-Related Dementias Focus
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.
2028 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) RFA-NS-21-003: Center without Walls for Mechanisms of Neurodegeneration in Frontotemporal Dementia (FTD) (U54 Clinical Trial Not Allowed) PAR-23-211: Mechanistic Investigations into ADRD Multiple Etiology Dementias (R01 - Clinical Trial Not Allowed) PAR-23-212: Investigating Distinct and Overlapping Mechanisms in TDP-43 Proteinopathies, including in LATE, FTD & other ADRDs (R01 - Clinical Trial Not Allowed) NOT-AG-24-033: Notice of Special Interest (NOSI): Selective Cell and Network Vulnerability in Aging and Alzheimer’s Disease 2.U In Progress DN 2019 ADRD Summit: Emerging Scientific Topics, Focus Area 1: TDP-43 Pathology in Common Dementias, Milestone 2 Press Release: Abnormal proteins found in the spinal fluid of people with ALS and frontotemporal dementia Workshop: Molecular Mechanisms and Pathobiology of TDP-43 in LATE and Alzheimer's Disease and Its Related Dementias Highlight: Abnormal proteins found in the spinal fluid of people with ALS and frontotemporal dementia Workshop: Molecular Mechanisms and Pathobiology of TDP-43 in LATE and Alzheimer's Disease and Its Related Dementias Research on Disease Mechanisms Select projects funded in FY21 University of Kentucky ADRC Neuropathology Core Select projects funded in FY22 2020
- Support at least one new initiative on 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.
The key accomplishments summary is current as of July 2022.