ECE2 and Cognitive impairment: Further in vitro analysis demonstrated that R186C or F751S mutant removed the activity of ECE2 that lead to impaired degradation of amyloid β. In vivo, preclinical studies on mouse models showed that R186C mutation caused the loss of ECE2 function that results in finding that ECE2 R186C proteins may lead to amyloid β accumulation forming neuritic plaque and cognitive deficits [57].