Surprisingly, while the TREM2 AD variants R47H, R62H, and T96K had previously shown small 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 and Table 1). Here, TREM2 is linked to Alzheimer disease.