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). This evidence concerns the gene NUP214 and Alzheimer disease.