Multimerization of TREM2 is impaired by Alzheimer's disease-associated variants.

Introduction: The immune receptor triggering receptor expressed on myeloid cells 2 (TREM2) is among the strongest genetic risk factors for Alzheimer's disease (AD) and is a therapeutic target. TREM2 multimers have been identified in crystallography and implicated in the efficacy of antibody therapeutics; however, the molecular basis for TREM2 multimerization remains poorly understood.

Methods: We used molecular dynamics simulations and binding energy analysis to determine the effects of AD-associated variants on TREM2 multimerization and validated with experimental results.