PLCG2 gene variants and their effects on Alzheimer's risk

Impact of PLCG2 Alzheimer's Disease Risk Variants on Microglia Biology and Disease Pathogenesis

NIH-funded research Indiana University Indianapolis · NIH-11176295

This project looks at whether two changes in the PLCG2 gene make Alzheimer’s disease more or less likely by studying how they change brain immune cells called microglia.

Quick facts

Grant typeR01 grant
Study typeNIH-funded research
Funding institutionIndiana University Indianapolis NIH-funded
Lab location1 site (Indianapolis, United States)
Project IDNIH-11176295 on NIH RePORTER

What this research studies

From a patient's point of view, researchers are using mouse models that carry human PLCG2 gene variants linked to higher or lower Alzheimer’s risk to see how those changes affect microglia behavior and disease features like plaque buildup and memory problems. They will compare a suspected risk variant (M28L) and a protective variant (P522R) to learn whether one reduces PLCG2 function while the other boosts it. The team will examine molecular signaling in microglia, brain pathology in the mice, and links between the gene changes and disease progression. The goal is to understand mechanisms so future therapies could target microglial pathways.

Who could benefit from this research

Good fit: This specific grant does not enroll people, but its results are most relevant to individuals with Alzheimer’s disease or those known to carry PLCG2 variants.

Not a fit: People without Alzheimer’s disease and those without PLCG2-related biology are unlikely to receive direct benefit from this project in the near term.

Why it matters

Potential benefit: If successful, this work could reveal new ways to modify immune-cell activity in the brain and point to targets for therapies that slow or prevent Alzheimer’s disease.

How similar studies have performed: Genetic studies have already linked the P522R PLCG2 variant to lower Alzheimer’s risk, but comprehensive functional tests in disease models remain relatively new.

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 disease dementiaAlzheimer syndromeAlzheimer's DiseaseAlzheimer's disease brain
Last reviewed 2026-06-13 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.