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

Area of Science:

• Neuroscience
• Immunology
• Genetics

Background:

• Triggering receptor expressed on myeloid cells 2 (TREM2) is crucial for myeloid cell function in the central nervous system and periphery.
• TREM2 mutations are linked to Nasu-Hakola disease and the R47H variant is a risk factor for late-onset Alzheimer disease.
• TREM2 is known to bind polyanionic molecules, but its specific protein ligands remain unidentified.

Purpose of the Study:

• To identify specific protein ligands for TREM2.
• To investigate the functional relationship between TREM2 and apolipoprotein E (ApoE) in the context of neurodegenerative diseases.

Main Methods:

• Utilized TREM2-Ig fusions to precipitate ApoE from cerebrospinal fluid and serum.
• Employed ELISA to detect binding of TREM2 to recombinant and immobilized ApoE.
• Assessed the impact of the R47H mutation and other mutations on TREM2-ApoE binding affinity.

Main Results:

• Demonstrated that TREM2 specifically binds apolipoprotein E.
• TREM2-Ig fusions effectively isolated ApoE from biological samples.
• The Alzheimer disease-associated R47H mutation significantly reduced TREM2's affinity for ApoE.

Conclusions:

• Established a direct molecular link between TREM2 and apolipoprotein E, two significant factors in Alzheimer disease.
• The findings provide insights into the pathogenesis of TREM2-associated neurodegenerative disorders, including Nasu-Hakola disease and Alzheimer disease.