TREM2 and Alzheimer disease: While these studies showed that TREM2 loss of function variant R47H was linked with increased neurofibrillary tangles and neuritic plaques in AD [32,33], Okuzono et al. [4] added that TREM2 loss was caused by proteases such as ADAM17, or ADAM10 and meprin β which inhibit TREM2-mediated phagocytosis.