Figure 3.

The involvement of TREM2 in post-TBI amyloid beta clearance. (A) Aβ released after TBI quickly forms into plaques and may bind to lipoproteins. TREM2 assists surrounding myeloid cells in sensing Aβ-lipoprotein complexes, engulfing and breaking down the Aβ, and recruiting other phagocytes to the site of injury. (B) In the case of TREM2 mutations or dysfunction, these cells may not be able to properly sense and clear Aβ or recruit other cells, so that more Aβ builds up over time and leads to plaque formation as seen in Alzheimer’s disease. (C) Another possibility is that in the absence of TREM2 signaling, other signaling pathways may predominate in myeloid cells. For example, when a complex of CD36 with a TLR4-TLR6 heterodimer senses Aβ, instead of phagocytosis, it leads to release of pro-inflammatory cytokines and chemokines that can induce upregulation of secretases in other cells, which are known to lead to increased production of Aβ.