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2015 Grants - Landreth
Roles of TREM2 in Alzheimer’s Disease Pathogenesis
Gary Landreth, Ph.D.
Case Western Reserve University
2015 Biological Underpinnings of Genetic Risk Factors in Alzheimer’s Disease Grant
Which immune cells in the brain express the TREM2 protein and how does this relate to the brain changes associated with Alzheimer’s disease?
During Alzheimer’s disease there is inflammation in the brain resulting from activation of the brain’s immune system. While this process can be protective, excess inflammation can be damaging to nerve cells. Recent research has found that certain variations in a gene called triggering receptor expressed on myeloid cells 2 (TREM2) increases the risk of Alzheimer’s disease. The TREM2 gene codes for the TREM2 protein that is found on certain immune cells. Until recently, TREM2 was thought to protect the brain by suppressing inflammation and encouraging a healthy immune response. However, recent studies have shown that mice genetically-engineered to lack TREM2 have fewer activated immune cells in the brain, less inflammation and fewer amyloid plaques, which are characteristic features of Alzheimer’s disease. This suggests that TREM2 may not be protective after all, and additional research is needed to better understand its role in Alzheimer’s disease.
Gary Landreth, Ph.D., and colleagues plan to study the role of TREM2 in brain inflammation and Alzheimer’s disease. Specifically they are interested in what types of immune cells have TREM2 – whether it is immune cells that are “resident” to the brain (called microglia) or immune cells that “infiltrate” the brain from the body. They will use Alzheimer’s-like mice that have been genetically-engineered to allow tracking of all immune cells that have TREM2. This will allow them to determine the type, number and exact location of the immune cells in the brain during disease progression. The research team will also use mice genetically-engineered to lack TREM2, either on resident or infiltrating immune cells, to determine the unique impact that these cell types have on the brain.
These studies will provide new information on the role of TREM2 and the immune system in Alzheimer’s disease. Importantly, these findings can help researchers identify potential targets for the development of novel treatments for preventing or treating Alzheimer’s disease.