Microglia, Trem2, and Neurodegeneration.

Shi Q, Gutierrez RA, Bhat MA

Neuroscientist 2025

Microglia are a specialized type of neuroimmune cells that undergo morphological and molecular changes through multiple signaling pathways in response to pathological protein aggregates, neuronal death, tissue injury, or infections. Microglia express Trem2, which serves as a receptor for a multitude of ligands enhancing their phagocytic activity. Trem2 has emerged as a critical modulator of microglial activity, especially in many neurodegenerative disorders. Human

5 Figures Extracted

Figure 1. PMC

Historical milestones in microglia-Trem2 research. Schematic illustration of the key milestone events from various research groups that contributed to...

Figure 2. PMC

Domain structure of the Trem2 protein and its association with Alzheimer disease (AD) risk. ( A ) Human Trem2 protein domain structure: this schematic...

Figure 3. PMC

Homeostasis of microglia during Alzheimer disease (AD) pathogenesis. At the earlier stages of AD, microglia are activated in response to the expressio...

Figure 4. PMC

Mammalian target of rapamycin (mTOR) regulates the expression of Trem2 in microglia. Loss of Tsc1 triggers mTOR activation, which in turn stimulates m...

Figure 5. PMC

Targeting Trem2 for therapeutic intervention in Alzheimer disease (AD) and neurological disorders. ( A ) Agonistic antibodies: antibodies such as 4D9,...