| First Author | Lessard CB | Year | 2018 |
| Journal | EMBO Mol Med | Volume | 10 |
| Issue | 11 | PubMed ID | 30341064 |
| Mgi Jnum | J:277861 | Mgi Id | MGI:6355593 |
| Doi | 10.15252/emmm.201809027 | Citation | Lessard CB, et al. (2018) High-affinity interactions and signal transduction between Abeta oligomers and TREM2. EMBO Mol Med 10(11) |
| abstractText | Rare coding variants in the triggering receptor expressed on myeloid cells 2 (TREM2) are associated with increased risk for Alzheimer's disease (AD), but how they confer this risk remains uncertain. We assessed binding of TREM2, AD-associated TREM2 variants to various forms of Abeta and APOE in multiple assays. TREM2 interacts directly with various forms of Abeta, with highest affinity interactions observed between TREM2 and soluble Abeta42 oligomers. High-affinity binding of TREM2 to Abeta oligomers is characterized by very slow dissociation. Pre-incubation with Abeta is shown to block the interaction of APOE In cellular assays, AD-associated variants of TREM2 reduced the amount of Abeta42 internalized, and in NFAT assay, the R47H and R62H variants decreased NFAT signaling activity in response to Abeta42. These studies demonstrate i) a high-affinity interaction between TREM2 and Abeta oligomers that can block interaction with another TREM2 ligand and ii) that AD-associated TREM2 variants bind Abeta with equivalent affinity but show loss of function in terms of signaling and Abeta internalization. |
