MAPT and Alzheimer disease: Therefore, although the amount of extracellular NH2htau required to affect synaptic functions is higher than the diffusive levels of tau found in AD patient CSF or in the conditioned media from neuronal cultures and in interstitial fluids, it’s more likely to assume that the secretion of soluble tau species through a synaptic mechanism would necessarily generate local concentrations at the release site, and likely site of action, which are significantly higher than its circulating levels [13].