Single-cell map of GRN-related frontotemporal dementia and related Alzheimer's changes
Single Cell Characterization of FTLD-GRN
Researchers are using single-cell methods to pinpoint how low Progranulin from GRN gene changes harms brain immune cells and neurons in people with GRN-linked frontotemporal dementia and some Alzheimer's cases.
Quick facts
| Grant type | R01 grant |
|---|---|
| Study type | NIH-funded research |
| Funding institution | University of California, San Francisco NIH-funded |
| Lab location | 1 site (San Francisco, United States) |
| Project ID | NIH-10700363 on NIH RePORTER |
What this research studies
This project will profile individual brain nuclei from mouse models and donated human frontal cortex and thalamus using single-nucleus RNA sequencing and chromatin-accessibility assays to see which cell types change when Progranulin (PGRN) is low. If you or a loved one has a GRN mutation or frontotemporal dementia, the team will compare your tissue to controls to link genetics to cell-level inflammation and TDP-43 protein clumps. The researchers focus on microglia (brain immune cells) that lose normal genes and become pro-inflammatory and on neurons that show TDP-43 pathology and degeneration. The goal is to identify specific cell pathways and biomarkers that could guide future targeted therapies.
Who could benefit from this research
Good fit: Ideal candidates include people with known GRN mutations, a clinical diagnosis of frontotemporal dementia, or Alzheimer's patients with suspected TDP-43 involvement who can donate brain tissue or provide related biospecimens.
Not a fit: Patients with dementias caused by unrelated mechanisms or without GRN/TDP-43 involvement may not receive direct benefit from this work.
Why it matters
Potential benefit: Could identify the precise cell types and molecular pathways driving neurodegeneration in GRN-related FTLD and some Alzheimer’s cases, pointing to targets or biomarkers for future treatments.
How similar studies have performed: Prior mouse models and small human postmortem single-cell studies—including the team's pilot data—have shown microglial activation and links to TDP-43, so this builds on promising but still early evidence.
Where this research is happening
San Francisco, United States
- University of California, San Francisco — San Francisco, United States (Active)
Researchers
- Principal investigator: Huang, Eric J — University of California, San Francisco
- Study coordinator: Huang, Eric J
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.