Apolipoprotein E Is a Ligand for Triggering Receptor Expressed on Myeloid Cells 2 (TREM2)

摘要: Several heterozygous missense mutations in the triggering receptor expressed on myeloid cells 2 (TREM2) have recently been linked to risk for a number of neurological disorders including Alzheimer disease (AD), Parkinson disease, and frontotemporal dementia. These discoveries re-ignited interest role neuroinflammation pathogenesis neurodegenerative diseases. TREM2 is highly microglia, resident immune central nervous system. Along with its adaptor protein, DAP12, regulates inflammatory cytokine release phagocytosis apoptotic neurons. Here, we report apolipoprotein E (apoE) as novel ligand TREM2. Using biochemical assay, demonstrated high-affinity binding apoE human The functional significance this was highlighted by increased apoE-bound N2a primary microglia manner that depends expression. Moreover, when AD-associated TREM2-R47H mutant used assays, vastly reduced. Our data demonstrate apoE-TREM2 interaction plays critical roles modulating neurons establish link between two proteins whose genes are strongly AD.