How loss of the TDP-43 protein harms prefrontal brain circuits in Alzheimer's and related dementias
Loss of TDP-43 disrupts the prefrontal neural activity and circuitry: relevance for TDP-43 linked ADRD
This work looks at how losing a protein called TDP‑43 changes brain signals and wiring in people with Alzheimer's disease and related dementias.
Quick facts
| Grant type | R01 grant |
|---|---|
| Study type | NIH-funded research |
| Funding institution | University of Wyoming NIH-funded |
| Lab location | 1 site (Laramie, United States) |
| Project ID | NIH-10795754 on NIH RePORTER |
What this research studies
Researchers will study how TDP‑43 loss causes the earliest changes in brain cell activity and networks that happen before neurons die, focusing on the prefrontal cortex. They will combine lab models, molecular studies of RNA splicing (including calcium channel genes), and recordings of neural activity to trace the chain of events from molecular change to circuit dysfunction. The team will use human-relevant data and tissue where available to link lab findings to the types of brain changes seen in Alzheimer's and Alzheimer-related dementias. The goal is to find molecular and circuit points that could be targeted to protect thinking and memory.
Who could benefit from this research
Good fit: People with a diagnosis of Alzheimer's disease or Alzheimer-related dementias, especially those with signs or testing suggesting TDP‑43 involvement or who are willing to contribute brain tissue or clinical data, would be most relevant.
Not a fit: People whose dementia is due to causes completely unrelated to TDP‑43 pathology, or healthy individuals without dementia, are unlikely to gain direct benefits from this project.
Why it matters
Potential benefit: If successful, this work could point to new targets to slow or prevent early brain circuit breakdown in Alzheimer's and related dementias.
How similar studies have performed: Prior research has linked TDP‑43 to worse outcomes in ALS, frontotemporal dementia, and a substantial fraction of Alzheimer's brains, but targeting its role in early circuit dysfunction is a newer and still largely untested approach.
Where this research is happening
Laramie, United States
- University of Wyoming — Laramie, United States (Active)
Researchers
- Principal investigator: Li, Yun — University of Wyoming
- Study coordinator: Li, Yun
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.