How TMEM106B, GRN and TDP-43 interact in frontotemporal dementia
The TMEM106B-GRN-TDP43 triad: leveraging human samples and humanized models to unravel FTLD-TDP disease mechanisms
Looking at how three proteins—TMEM106B, progranulin (GRN), and TDP-43—work together to better understand frontotemporal dementia in people who develop early-onset dementia.
Quick facts
| Grant type | R01 grant |
|---|---|
| Study type | NIH-funded research |
| Funding institution | Flanders Interuniv Inst Biotechnology NIH-funded |
| Lab location | 1 site (Gent, Belgium) |
| Project ID | NIH-11189602 on NIH RePORTER |
What this research studies
This project uses human brain tissue samples and humanized lab models to uncover why TDP-43 protein clumps form in frontotemporal lobar degeneration (FTLD-TDP). Researchers will compare samples from people with GRN mutations and different TMEM106B genetic variants and will build humanized cell and animal models that better reflect human microglia and neurons. Because standard mouse models do not reproduce the TDP-43 pathology seen in patients, the team will introduce human genetic elements and patient-derived materials to recreate disease features. The goal is to reveal how these genetic factors interact to cause neurodegeneration and to create better models for testing future therapies.
Who could benefit from this research
Good fit: People diagnosed with frontotemporal dementia, carriers of GRN mutations, or family members at risk for FTLD-TDP would be the best candidates to provide samples or take part.
Not a fit: People whose dementia is clearly due to Alzheimer's disease or other non-TDP-43 causes may not directly benefit from this research.
Why it matters
Potential benefit: If successful, this work could produce more accurate human-based models and point to new targets for diagnostics or treatments for frontotemporal dementia.
How similar studies have performed: Previous GRN-deficient mouse studies caused neuroinflammation but did not produce the TDP-43 brain clumps seen in patients, so using human samples and humanized models is a newer approach to address that shortcoming.
Where this research is happening
Gent, Belgium
- Flanders Interuniv Inst Biotechnology — Gent, Belgium (Active)
Researchers
- Principal investigator: Rademakers, Rosa — Flanders Interuniv Inst Biotechnology
- Study coordinator: Rademakers, Rosa
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.