MAPT and Cognitive impairment: As activated GSK-3β is involved in phosphorylating tau, this provides another important mechanism by which CaN activation could lead to elevated phospho-tau levels and potentially the formation of NFT's seen in the brains of TBI and AD patients which correlates with synaptic dysfunction and cognitive impairment (see Reese and Taglialatela, 2011) (Figure 4).