FIGURE 6.

Scheme of the stages of molecular tau processing. (A) Intact tau molecule shown. (B) On intact tau protein occurs the first phosphorylation in Thr231. This phosphorylation is decisive for the first conformational change evidenced by the TG-3 antibody (C). (D) The amino acids 202 and 205 (AT8) are phosphorylated, which favors the phosphorylation in amino acids 212 and 214 (AT100). It generates the second pathological conformational change in tau (E). The set of these two regional conformational changes favors the folding of the N-portion, causing the regional conformational change recognized by the Alz-50 antibody (epitopes 2–10 and 312–322) (F). (G) In pre-neurofibrillary tangles (NFTs), there is a high activity of caspase-3, which acts once the tau protein is phosphorylated in pT231.