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J Biol Chem. 2015 Oct 23;290(43):26033-42. doi: 10.1074/jbc.M115.677286. Epub 2015 Sep 15.

The Triggering Receptor Expressed on Myeloid Cells 2 Binds Apolipoprotein E.

Author information

  • 1From the Department of Immunobiology and Microbial Sciences, The Scripps Research Institute, Jupiter, Florida 33458 cbailey@scripps.edu.
  • 2From the Department of Immunobiology and Microbial Sciences, The Scripps Research Institute, Jupiter, Florida 33458.

Abstract

The triggering receptor expressed on myeloid cells 2 (TREM2) is an Ig-like V-type receptor expressed by populations of myeloid cells in the central nervous system and periphery. Loss-of-function mutations in TREM2 cause a progressive, fatal neurodegenerative disorder called Nasu-Hakola disease. In addition, a TREM2 R47H coding variant was recently identified as a risk factor for late-onset Alzheimer disease. TREM2 binds various polyanionic molecules but no specific protein ligands have been identified. Here we show that TREM2 specifically binds apolipoprotein E, a well established participant in Alzheimer disease. TREM2-Ig fusions efficiently precipitate ApoE from cerebrospinal fluid and serum. TREM2 also binds recombinant ApoE in solution and immobilized ApoE as detected by ELISA. Furthermore, the Alzheimer disease-associated R47H mutation, and other artificial mutations introduced in the same location, markedly reduced the affinity of TREM2 for ApoE. These findings reveal a link between two Alzheimer disease risk factors and may provide important clues to the pathogenesis of Nasu-Hakola disease and other neurodegenerative disorders.

© 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

KEYWORDS:

Alzheimer disease; Nasu-Hakola disease; PLOSL; TREM2; apolipoprotein E (ApoE); genetic polymorphism; high-density lipoprotein (HDL); myeloid cell; neurodegenerative disease

PMID:
26374897
[PubMed - indexed for MEDLINE]
PMCID:
PMC4646256
[Available on 2016-10-23]
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