Finally, TREM2 activity can be impaired by its excessive shedding from the microglial cell surface, triggered by the α-secretases ADAM10 and 17 (a disintegrin and metalloproteinase domain-containing protein 10 and 17), in a specific AD-associated variant (Schlepckow et al., 2017; Thornton et al., 2017). This evidence concerns the gene TREM2 and Alzheimer disease.