TREM2 and TYROBP in Alzheimer's brain network changes
Official title: Roles of TREM2 and TYROBP in AD-related Network Hyperexcitability
Funded at J. David Gladstone Institutes · NIH-11463412 · Data updated 2026-11-12
This grant looks at how microglial proteins TREM2 and TYROBP influence brain network excitability in people with Alzheimer's disease and related dementias.
Quick facts
| Grant type | R01 grant |
|---|---|
| Study type | NIH-funded research |
| Funding institution | J. David Gladstone Institutes NIH-funded |
| Lab location | 1 site (San Francisco, United States) |
| Project start | September 1, 2023 |
| Project end | August 31, 2028 |
| Funding year | 2026 |
| Award (this year) | $944,363 |
| NIH project number | 4R01AG083079-02 |
| Project ID | NIH-11463412 on NIH RePORTER |
Who could benefit from this research
✓Could help
Ideal candidates are individuals with or at risk for Alzheimer’s disease or related dementias, particularly those with biomarkers or family history suggesting TREM2/TYROBP-related mechanisms.
✕Less likely to help
People without AD or related dementias or without the specific microglial pathways studied may not directly benefit.
What this research studies
Researchers will study how the TREM2-TYROBP signaling axis in brain immune cells affects neural network activity that may contribute to cognitive decline in AD. The work combines genetic models and disease-relevant contexts to understand why microglia influence brain circuits as AD pathology develops. Findings could point to new ways to protect brain networks in people with AD by targeting microglial signaling. The project aims to connect molecular changes in microglia with functional brain changes seen in patients and animal models.
Why it matters
Potential benefit: If successful, the work could guide new therapeutic strategies to stabilize brain networks and slow cognitive decline in AD.
How similar studies have gone: Prior studies have linked microglial receptors to AD pathology and network changes, with some results showing consistent functional links and others showing discrepancies.
Where this research is happening
-
J. David Gladstone Institutes
San Francisco, United States Active
Researchers
- Principal investigator: Mucke, Lennart — J. David Gladstone Institutes
- Study coordinator: Mucke, Lennart
Related research
Other NIH-funded projects on the same topics.
-
HOPE: a new approach to silencing HIV and preventing rebound
A large NIH grant is testing a combination strategy to turn off HIV genes in people on treatment so the virus stays gone and health improves.
-
Undo HIV: Understanding and targeting the active HIV reservoir
Aims to map and ultimately eliminate the HIV cells that stay active despite therapy to improve long-term control of HIV in people living with HIV.
-
Commensal respiratory viruses and how they interact with the human airway
A small NIH grant is exploring how the normal viruses living in our airways interact with our cells to stay harmless and support healthy breathing.
-
Targeted delivery systems to edit blood stem cells
Aims to safely deliver genome-editing tools to blood stem cells to treat diseases like acute myeloid leukemia.
-
Regionally Specific Transplants to Restore Breathing After Cervical Spine Injury
A patient-focused look at a study that aims to repair breathing circuits after cervical spinal cord injury using stem-cell–derived nerve cells and targeted neuromodulation.
-
Machine learning to understand how noncoding DNA variants affect heart development
A new AI-based tool is being developed to predict how noncoding genetic changes influence heart development and contribute to congenital heart disease in children.
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.