It is not currently known how Aβ and Tau pathology are linked, however, the amyloid cascade hypothesis suggests that Aβ pathology leads to the other hallmarks of AD, including the spread of NFTs (Selkoe and Hardy, 2016) and recent work suggests changes in neuronal excitability and calcium (Ca2+) signaling may be important for their connection and disease progression (Spires-Jones and Hyman, 2014; Wu et al., 2016), but exactly how remains unknown. The gene discussed is MAPT; the disease is Alzheimer disease.