TDP-43 protein changes in Alzheimer’s, frontotemporal dementia, and ALS

Investigating the role of TDP-43 mislocalization, structure, and post-translational modifications in the neuropathologically heterogeneous TDP-43 proteinopathies

NIH-funded research Indiana University Indianapolis · NIH-11321167

This project looks at how different shapes and chemical changes of the TDP-43 protein may relate to memory, behavior, and movement problems in people with Alzheimer's disease, frontotemporal dementia, or ALS.

Quick facts

Grant typeR01 grant
Study typeNIH-funded research
Funding institutionIndiana University Indianapolis NIH-funded
Lab location1 site (Indianapolis, United States)
Project IDNIH-11321167 on NIH RePORTER

What this research studies

Researchers will examine brain tissue and related samples from people with Alzheimer’s disease, frontotemporal dementia, LATE, and ALS to see where and how TDP-43 protein is misplaced and altered. The team will use detailed tissue staining, digital spatial mapping, genetic testing, and high-resolution cryo-electron microscopy to view TDP-43 structures and chemical tags. They will compare different neuropathologic subtypes to find patterns of protein structure, post-translational modifications, and seeding behavior that might explain regional brain damage and symptom differences. Results across patient samples will be linked back to clinical features to identify consistent signatures.

Who could benefit from this research

Good fit: Ideal participants are people diagnosed with Alzheimer's disease, frontotemporal dementia (FTLD-TDP), LATE, or ALS, or their families willing to donate brain tissue, clinical data, or biospecimens.

Not a fit: People without neurodegenerative disease or whose condition is caused by non–TDP-43 pathology are unlikely to get direct benefit from this specific work.

Why it matters

Potential benefit: If successful, this work could reveal biological markers and targets that help diagnose TDP-43–related disease earlier and guide development of future treatments.

How similar studies have performed: Previous work has shown TDP-43 aggregates in ALS and some dementias, but combining high-resolution structural imaging with broad molecular mapping of TDP-43 changes across disease types is a relatively new approach.

Where this research is happening

Indianapolis, 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 dementiaAlzheimer syndromeAlzheimer's DiseaseAmyotrophic Lateral Sclerosis Motor Neuron Disease
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.