TREM2 and Alzheimer disease: For example, shRNA-mediated Trem2 downregulation [33], Trem2 haploinsufficiency [18, 55], Trem2 deletion [7] in mouse tauopathy models, or Trem2 deletion in 5xFAD mouse brain injected with tau derived from human AD brain (“AD-tau”) [21] can aggravate tau pathology which together, suggests that Trem2 normally restrains pathological effects associated with tau.