TDP‑43 related dementias: causes and treatments
Disease Mechanism and Therapy in TDP-43 Proteinopathies and Dementias
This project works on stopping harmful clumping of a brain protein called TDP‑43 to help people with Alzheimer‑like dementia, LATE, frontotemporal dementia, or ALS‑related dementia.
Quick facts
| Grant type | R01 grant |
|---|---|
| Study type | NIH-funded research |
| Funding institution | University of California, San Diego NIH-funded |
| Lab location | 1 site (La Jolla, United States) |
| Project ID | NIH-11169824 on NIH RePORTER |
What this research studies
Researchers are studying how aging weakens the cell’s protein-clearance machinery (the proteasome), which lets the TDP‑43 protein leave the nucleus, form liquid droplets, and then harden into toxic clumps in brain cells. The team uses lab models, biochemical methods, and advanced mass spectrometry with proximity labeling to map proteins that interact with TDP‑43. They are focusing on a small heat‑shock protein (HSPB1) that can enter TDP‑43 droplets and prevent or reverse their conversion to harmful fibrils. Findings may rely on human brain tissue or clinically relevant samples alongside cellular and animal experiments to link the basic biology to patient disease.
Who could benefit from this research
Good fit: Ideal candidates are older adults diagnosed with Alzheimer disease dementia, LATE, frontotemporal dementia, or ALS‑related dementia who can provide clinical information or biological samples or who may be eligible for future treatment trials.
Not a fit: People whose cognitive problems are caused by non‑TDP‑43 processes or who cannot provide samples or participate in follow‑up are unlikely to benefit directly from this research.
Why it matters
Potential benefit: If successful, this work could point to new therapies that prevent or reverse TDP‑43 clumping and slow or stop cognitive decline in multiple dementias.
How similar studies have performed: Prior laboratory and preclinical studies support the idea that heat‑shock proteins and proteasome function influence TDP‑43 behavior, but translating these findings into proven patient treatments is still untested.
Where this research is happening
La Jolla, United States
- University of California, San Diego — La Jolla, United States (Active)
Researchers
- Principal investigator: Cleveland, Don W — University of California, San Diego
- Study coordinator: Cleveland, Don W
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.