Furthermore, tau hyperphosphorylation is not dependent upon the administration of a protein phosphatase inhibitor, since this has been observed after injection of saline into the brain [32,137] and after transient cerebral ischaemia [138,139], and physical damage to the brain leads not only to hyperphosphorylation of tau, but also other cerebral changes characteristic of Alzheimer’s disease [140]. Here, MAPT is linked to early-onset autosomal dominant Alzheimer disease.