Progranulin loss and how it disrupts brain lipid and lysosome function in frontotemporal dementia
Endolysosomal trafficking and lipid metabolism defects in FTLD
Looking at whether low progranulin causes lipid buildup and broken lysosome traffic that harm brain cells in people with frontotemporal dementia and related dementias.
Quick facts
| Grant type | R01 grant |
|---|---|
| Study type | NIH-funded research |
| Funding institution | Washington University NIH-funded |
| Lab location | 1 site (Saint Louis, United States) |
| Project ID | NIH-11309686 on NIH RePORTER |
What this research studies
You'll learn how loss of progranulin (GRN) — a change seen in some frontotemporal dementia and related conditions — leads to lipid buildup and faulty lysosome traffic in brain immune cells (microglia). The team uses mice engineered to carry human GRN mutations, human-cell experiments, detailed lipid analyses, and subcellular fractionation to trace where lipids get stuck and how that harms neurons and promotes TDP-43 protein clumps. They also test how blocking immune signals (complement, TNFa, IL-1a) changes the outcome and whether restoring lysosomal lipid trafficking can prevent neuron loss. The goal is to identify mechanisms and targets that could lead to treatments to protect memory and behavior in affected people.
Who could benefit from this research
Good fit: People with known GRN mutations, family histories of frontotemporal dementia, or clinical features suggesting TDP-43–related dementia would be the most relevant candidates to follow or donate samples to related efforts.
Not a fit: Patients whose dementia is caused by unrelated mechanisms (for example purely vascular dementia without TDP-43 or progranulin links) are unlikely to benefit directly from these findings in the near term.
Why it matters
Potential benefit: Could point to new drug targets or strategies to stop lipid buildup and protect neurons in FTLD, Alzheimer-related dementia, and LATE.
How similar studies have performed: Prior animal and cell studies have linked progranulin loss to inflammation and neurodegeneration, and blocking complement or cytokines gave partial benefits, making this focused look at lipids and lysosomes a newer direction.
Where this research is happening
Saint Louis, United States
- Washington University — Saint Louis, United States (Active)
Researchers
- Principal investigator: Huang, Eric J — Washington University
- 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.