TREM2 and Alzheimer disease: The immune system is exquisitely modulated by a complex set of checks and balances in which AD genes such as CD33, TREM1, and TREM2 are contributing to regulate the level of activation9, and, as seen in other immune functional programs, small differences in the level of receptor engagement or the presence of co-stimulatory molecules can result in dramatically different responses that can sometimes be the opposite of an anticipated response.