How the protein TDP-43 may make Alzheimer's worse

Mechanisms of TDP-43 neurotoxicity in Alzheimer's disease

NIH-funded research VA Puget Sound Healthcare System · NIH-11212833

Researchers are looking at how the protein TDP-43 works with tau to make Alzheimer’s disease worse in older adults.

Quick facts

Grant typeNIH-funded research
Study typeNIH-funded research
Funding institutionVA Puget Sound Healthcare System NIH-funded
Lab location1 site (Seattle, United States)
Project IDNIH-11212833 on NIH RePORTER

What this research studies

This project uses tiny worm models to see how two proteins linked to Alzheimer’s—tau and TDP-43—act together to damage nerve cells. The team will build worms carrying human protein variants and use precise gene editing plus sensitive behavior and imaging tests to watch what happens. They will pinpoint which parts of each protein drive the worst effects and how the proteins accumulate in cells. Although done in lab models, the findings could explain steps that speed memory loss in people with Alzheimer’s.

Who could benefit from this research

Good fit: People with Alzheimer’s disease—especially older adults with faster memory decline or signs of TDP-43-related brain changes—are most relevant to this research.

Not a fit: Patients without Alzheimer’s disease or those whose condition does not involve TDP-43 are unlikely to benefit directly from this laboratory-focused work.

Why it matters

Potential benefit: If successful, the work could reveal biological targets for new treatments to slow or prevent cognitive decline in people with Alzheimer’s who have TDP-43 co-pathology.

How similar studies have performed: Earlier experiments in C. elegans showed that tau and TDP-43 together increase neurotoxicity, so this project builds on that promising but still early evidence.

Where this research is happening

Seattle, United States

Researchers

About this research

  1. This is an active NIH-funded research project — typically early-stage science, not a clinical trial accepting patient enrollment.
  2. Some NIH-funded labs run parallel clinical studies or seek volunteers for related work. To check, contact the principal investigator or institution listed above.
  3. For full project details, budget, and progress reports, visit the official NIH RePORTER page below.
Conditions Alzheimer disease dementia
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.