The Alzheimer's disease risk factors apolipoprotein E and TREM2 are linked in a receptor signaling pathway.

ABSTRACT:

Background

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.

Methods

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.

Results

ApoE was found to be an agonist to human TREM2 with EC₅₀ in the low nM

SUBMITTER: Jendresen C 

PROVIDER: S-EPMC5360024 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature