TREM2 and Alzheimer disease: In addition to amyloid, studies are focusing on tau hyperphosphorylation, neuroinflammation through triggering receptor on myeloid cells 2 (TREM2) and NLR family pyrin domain containing 3 (NLRP3) and growth factor-mediated synaptic plasticity through brain-derived neurotrophic factor (BDNF).<h4>Conclusions</h4>AD treatment has entered the new era that demands a paradigm shift from monotherapies to multi-target cocktails.