Trem2 Enhances Demyelination in the Mouse Model of Leukoencephalopathy.

Colony-stimulating factor-1 receptor (CSF-1R)-related leukoencephalopathy (CRL) is a neurodegenerative disease that triggers early demyelination, leading to an adult-onset dementia. Triggering receptor expressed on myeloid cells-2 (TREM2) is a microglial receptor that promotes the activation of microglia and phagocytic clearance of apoptotic neurons and myelin debris. We investigated the role of Trem2 in the demyelination observed in the mouse model of CRL. We show that elevation of expression and callosal demyelination occur in 4-5-month-old mice, prior to the development of symptoms. Absence of in the mouse attenuated myelin pathology and normalized microglial densities and morphology in the corpus callosum. absence also prevented axonal degeneration and the loss of cortical layer V neurons observed in mice. Furthermore, the absence of Trem2 prevented the accumulation of myelin-derived lipids in macrophages and reduced the production of TNF-α after myelin engulfment. These data suggest that TREM2 contributes to microglial dyshomeostasis in CRL.