Immune system interactions in FTD caused by GRN mutations

Role of central and peripheral immune crosstalk in FTD-Grn neurodegeneration

NIH-funded research Indiana University Indianapolis · NIH-10699941

This project looks at how immune cells in the brain and blood might damage neurons in people with frontotemporal dementia caused by progranulin (GRN) mutations.

Quick facts

Grant typeR01 grant
Study typeNIH-funded research
Funding institutionIndiana University Indianapolis NIH-funded
Lab location1 site (Indianapolis, United States)
Project IDNIH-10699941 on NIH RePORTER

What this research studies

Researchers will use cells made from patient stem cells (iPSC-derived neurons, microglia, and monocytes/macrophages) alongside mouse models to study how peripheral immune cells communicate with brain microglia in GRN-related FTD. They will model blood-brain barrier leakage and test whether circulating monocytes can enter the brain and drive synapse loss or neuron dysfunction. Experiments will include 3D cell cultures and comparisons between human-derived cells and animal tissues to link molecular changes to neuron health. The team will measure progranulin levels, inflammatory signaling, and markers of neuronal integrity to map harmful immune crosstalk.

Who could benefit from this research

Good fit: People with frontotemporal dementia who carry progranulin (GRN) mutations or family members known to carry GRN mutations would be the most relevant candidates for related sample donation or future trials.

Not a fit: People with dementia caused by unrelated genes or non-GRN forms of Alzheimer's-related dementias may not benefit directly from findings specific to GRN-linked FTD.

Why it matters

Potential benefit: If successful, this work could reveal immune-driven mechanisms to target with treatments or biomarkers for GRN-related FTD.

How similar studies have performed: Prior studies using iPSC and mouse models have identified roles for progranulin and microglia in FTD, but studying peripheral immune cell infiltration and crosstalk in GRN-FTD is a newer and less-tested 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's disease and related dementiaAlzheimer's disease and related disordersAlzheimer's disease or a related dementiaAlzheimer's disease or a related disorderAlzheimer's disease or related dementia
Last reviewed 2026-06-15 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.