Related Experiment Video
Updated: Jul 24, 2026
Preparation of Oligomeric β-amyloid1-42 and Induction of Synaptic Plasticity Impairment on Hippocampal Slices
Published on: July 14, 2010
Functional insights from biophysical study of TREM2 interactions with apoE and Aβ1-42
Daniel L Kober1,2, Melissa D Stuchell-Brereton3, Colin E Kluender2,4
1Molecular Microbiology and Microbial Pathogenesis Program.
Introduction:
Triggering receptor expressed on myeloid cells-2 (TREM2) is an immune receptor expressed on microglia that also can become soluble (sTREM2). How TREM2 engages different ligands remains poorly understood.
Methods:
We used comprehensive biolayer interferometry (BLI) analysis to investigate TREM2 and sTREM2 interactions with apolipoprotein E (apoE) and monomeric amyloid beta (Aβ) (mAβ42).
Results:
TREM2 engagement of apoE was protein mediated with little effect of lipidation, showing slight affinity differences between isoforms (E4 > E3 > E2). Another family member, TREML2, did not bind apoE. Disease-linked TREM2 variants within a "basic patch" minimally impact apoE binding. Instead, TREM2 uses a unique hydrophobic surface to bind apoE, which requires the apoE hinge region. TREM2 and sTREM2 directly bind mAβ42 and potently inhibit Aβ42 polymerization, suggesting a potential role for soluble sTREM2 in preventing AD pathogenesis.
Discussion:
These findings demonstrate that TREM2 has at least two ligand-binding surfaces that might be therapeutic targets and uncovers a potential function for sTREM2 in directly inhibiting Aβ polymerization.
Insights
Triggering receptor expressed on myeloid cells-2 (TREM2) binds apolipoprotein E via a unique hydrophobic surface. Soluble TREM2 (sTREM2) also binds amyloid beta, potentially inhibiting Alzheimer's disease pathogenesis.
Area of Science:
- Neuroscience
- Immunology
- Biochemistry
Background:
- Triggering receptor expressed on myeloid cells-2 (TREM2) is a microglial immune receptor with a soluble form (sTREM2).
- Ligand interactions of TREM2 are not well understood.
Purpose of the Study:
- To investigate TREM2 and sTREM2 interactions with apolipoprotein E (apoE) and monomeric amyloid beta (Aβ).
Main Methods:
- Comprehensive biolayer interferometry (BLI) analysis was employed.
- Interactions with apoE isoforms and monomeric Aβ42 (mAβ42) were assessed.
Main Results:
- TREM2 binds apoE through a protein-mediated interaction involving a hydrophobic surface, with minor variations across apoE isoforms (E4>E3>E2).
- Disease-linked TREM2 variants minimally affected apoE binding.
- TREM2 and sTREM2 directly bind mAβ42 and inhibit Aβ42 polymerization.
Conclusions:
- TREM2 possesses at least two distinct ligand-binding surfaces with therapeutic potential.
- sTREM2 may play a role in preventing Alzheimer's disease by inhibiting Aβ polymerization.
