To this point, biochemical and functional outcomes in vivo measures further confirm that 12A12mAb: (i) does not specifically interact with the abundant intracellular pool of endogenous normal full-length tau protein whose steady-state level is unchanged in hippocampus after its i.v. delivery in Tg-Alzheimer’s disease mice regardless of the genetic backgrounds; (ii) is harmless when injected in healthy, cognitive-intact WT mice, despite the ability of successfully penetrating/reaching the brain in its biologically active (antigen-competent) state under physiological settings. Here, MAPT is linked to Alzheimer disease.