Fig. 2

Biochemical analysis of additional rare TREM2 variants identified in the Alzheimer’s Disease Sequencing Project (ADSP) replication cohort. a and b Five additional rare TREM2 variants identified in patients with AD were analyzed as in Fig. 1. All variants showed normal maturation and mobility by immunoblot analysis. CHC was used as a loading control for the cell lysates and to control for non-specific biotinylation (as above). Whole-cell lysate and cell surface biotinylation analysis indicated that variants S31F, R47C and E151K showed significantly reduced overall expression, while S31F and R47C showed significantly reduced surface expression. Variant A28V specifically showed increased surface expression. Variants Y38C and R47H were used, respectively, as internal controls for severe or modest reductions in cell surface expression (* p < 0.05, ** p < 0.01 by ANOVA followed by Holm-Sidak post hoc test). Results were quantified from 3–4 independent experiments for each variant