TREM2 and Alzheimer disease: Although some ADAM10 variants have been associated with higher susceptibility to develop the sporadic form of AD [66], a clear genetic correlation of α-secretase haploinsufficiency with clinical symptoms remains to be established; however, variants in TREM2, such as R47H and R62H, have been associated with decreased metabolic function (glycolysis, ATP levels, mTOR activation), leading to a reduction of Aβ toxicity and Aβ plaque formation [65].