The Triggering Receptor Expressed on Myeloid Cells 2: “TREM-ming” the Inflammatory Component Associated with Alzheimer's Disease

Figure 3

A central role for microglia in Alzheimer’s disease is dependent upon a functional TREM2 receptor. Microglia represent one of the three classes of glia cells, whose primary function is to act as a major line of active immune defense in the CNS. In AD, microglia (top) and astrocytes (bottom) function in phagocytosis and in this regard help clear the brain of beta-amyloid deposits and apoptotic cells as well as any cellular debris. The important actions of microglia appear to be mediated through activation of the TREM2 receptor whose few known roles include suppressing inflammation and stimulating phagocytosis. As shown recently, variants in the TREM2 receptor have been discovered, and it has been suggested that the change in sequence leads to a loss of receptor function. It has been hypothesized that the loss of TREM2 activity has two major consequences: (1) decreased ability of microglia to remove extracellular deposits of beta-amyloid and (2) enhanced neuroinflammation. The loss of TREM2 function and altered immune responses by microglia may explain the increased risk for AD for individuals carrying the heterozygous mutations in TREM2.