How PAD4 changes a brain protein in Alzheimer’s and LATE dementia
Emerging role of PAD4 mediated TDP-43 citrullination in the neuropathology of LATE and Alzheimer’s Disease Related Dementias
This project looks at whether an enzyme called PAD4 makes a chemical change to the brain protein TDP‑43 that leads to harmful clumping in people with Alzheimer’s disease and LATE dementia.
Quick facts
| Grant type | R01 grant |
|---|---|
| Study type | NIH-funded research |
| Funding institution | University of Kentucky NIH-funded |
| Lab location | 1 site (Lexington, United States) |
| Project ID | NIH-11298956 on NIH RePORTER |
What this research studies
Researchers will examine brain tissue from people with Alzheimer’s and LATE to see where PAD4 and citrullinated TDP‑43 appear in the human brain. They will use a new mouse model that mimics TDP‑43 changes and lab-grown neuronal cells to study how PAD4 causes TDP‑43 to move out of the nucleus and form toxic clumps. The team will test genetic and molecular changes to PAD4 activity and measure resulting nerve cell damage and memory-related effects in mice. Together these approaches aim to connect the molecular change to brain damage and cognitive decline.
Who could benefit from this research
Good fit: People living with Alzheimer’s disease or signs of LATE, or families willing to donate brain tissue or participate in related sample collection, would be the candidates for contributing to this work.
Not a fit: People whose dementia is driven by causes unrelated to TDP‑43 pathology may not benefit from PAD4‑focused approaches.
Why it matters
Potential benefit: If successful, the work could point to PAD4 or citrullinated TDP‑43 as new targets for treatments that slow or prevent TDP‑43–related dementia.
How similar studies have performed: TDP‑43 has been linked to several dementias before, but targeting PAD4‑mediated citrullination of TDP‑43 is a novel idea that has only early experimental support.
Where this research is happening
Lexington, United States
- University of Kentucky — Lexington, United States (Active)
Researchers
- Principal investigator: Selenica, Maj-Linda B — University of Kentucky
- Study coordinator: Selenica, Maj-Linda B
About this research
- This is an active NIH-funded research project — typically early-stage science, not a clinical trial accepting patient enrollment.
- Some NIH-funded labs run parallel clinical studies or seek volunteers for related work. To check, contact the principal investigator or institution listed above.
- For full project details, budget, and progress reports, visit the official NIH RePORTER page below.