biostudies-literatureJendresen CNorges ForskningsrådHelse Sør-Øst RHFAnders Jahres Fond til Vitenskapens FremmeUniversitetet i Oslo59https://www.ebi.ac.uk/biostudies/studies/S-EPMC5360024biostudies-literatureUnknown14(1)<h4>Background</h4>Triggering receptor expressed on myeloid cells 2 (TREM2) and apolipoprotein E (APOE) are genetically linked to Alzheimer's disease. Here, we investigated whether human ApoE mediates signal transduction through human and murine TREM2 and sought to identify a TREM2-binding domain in human ApoE.<h4>Methods</h4>To investigate cell signaling through TREM2, a cell line was used which expressed an NFAT-inducible β-galactosidase reporter and human or murine TREM2, fused to CD8 transmembrane and CD3ζ intracellular signaling domains. ELISA-based binding assays were used to determine binding affinities of human ApoE isoforms to human TREM2 and to identify a TREM2-binding domain in ApoE.<h4>Results</h4>ApoE was found to be an agonist to human TREM2 with EC₅₀ in the low nMJournal of neuroinflammationThe Alzheimer's disease risk factors apolipoprotein E and TREM2 are linked in a receptor signaling pathway.PMC53600242372502013016240316Arskog VDaws MRNilsson LNJendresen CfalseThe Alzheimer's disease risk factors apolipoprotein E and TREM2 are linked in a receptor signaling pathway.<h4>Background</h4>Triggering receptor expressed on myeloid cells 2 (TREM2) and apolipoprotein E (APOE) are genetically linked to Alzheimer's disease. Here, we investigated whether human ApoE mediates signal transduction through human and murine TREM2 and sought to identify a TREM2-binding domain in human ApoE.<h4>Methods</h4>To investigate cell signaling through TREM2, a cell line was used which expressed an NFAT-inducible β-galactosidase reporter and human or murine TREM2, fused to CD8 transmembrane and CD3ζ intracellular signaling domains. ELISA-based binding assays were used to determine binding affinities of human ApoE isoforms to human TREM2 and to identify a TREM2-binding domain in ApoE.<h4>Results</h4>ApoE was found to be an agonist to human TREM2 with EC₅₀ in the low nM2017-01-01T00:00:00Z2017 Mar2025-04-04T12:39:27.447Z2019-03-27T02:39:10ZS-EPMC53600242832042410.1186/s12974-017-0835-4