CDK5 and Alzheimer disease: Aluminum has been examined for its broad neurotoxic effects and close relationship with AD, which promote tau hyperphosphorylation, aggregation, and neurofibrillary tangle formation in AD brains (by activating tau kinases CDK5 and GSK3β), accumulate in microglia and induce proinflammatory cytokines, bind to Aβ and induce its aggregation, stimulate iron-induced membrane lipid peroxidation and oxidative damage, decrease the activity of antioxidant enzymes, and interact with AChE on γ-peripheral sites to enhance enzymatic activity, resulting in reduced neurotransmission [12, 59, 60].