Surprisingly, while the TREM2 AD variants R47H, R62H, and T96K had previously shown slight decreases in binding affinity for apoE4 (2–3 fold decrease in KD, Table 1), we found that AD risk variant D87N showed a dramatic 11-fold increase in affinity for apoE4 (KD = 25 nM; Fig. 2F; Table 1). Here, APOE is linked to Alzheimer disease.