Fig. 2.

Schematic representation illustrating the involvement of TNAP in the progression of Alzheimer's disease. First, tau protein reaches the interstitial space as a consequence of an initial undetermined injury or by its own vesicular release under physiological conditions. This tau protein is dephosphorylated by TNAP becoming an active ligand of muscarinic receptors. The activation of muscarinic receptors by tau has three main consequences; an increase of intracellular level of calcium and hyperphosphorylated tau, and an increase of TNAP levels. Subsequently of these effects, a positive feedback loop is generated in which the final consequence is cell death. With the rupture of the plasma membrane after the cell death, the intracellular contents are released to the interstitial space, increasing the extracellular levels of hyperphosphorylated tau. The NFTs (intracellular neurofibrillary tangles) suffer slow disassembly and degradation, allowing the proteins to reach distant brain regions that results in spreading of this neurodegenerative process.