MAPT and Cognitive impairment: Since it is well known that pTau accumulation in the brain occurs years before the onset of cognitive impairment [32], and considering that it was also reported that acute phosphorylated tau (pTau) protein accumulation caused by a brain injury leads to a significant decrease in total plasma AP activity [33], it could be suggested that the reduction in TNAP plasma activity observed in CU may be linked to the initial brain pTau accumulation.