DIFFERENTIAL SENSITIVITY PROTEOLYSIS BY BRAIN CALPAIN OF ADULT HUMAN-TAU, FETAL HUMAN-TAU AND PHF-TAU

Reduced turn-over of tau by calpains is a possible mechanism to facili tate the incorporation into paired helical filaments (PHFs) in Alzheim er's disease. The present study shows that the differently phosphoryla ted fetal tan isoforms are all rapidly proteolysed to an equal extent by human brain m-calpain. This result argues against the hypothesis th at this type of fetal phosphorylation is involved in reducing tau turn -over by calpain in Alzheimer's disease. Adult and fetal tau fragments in vitro generated by m-calpain, but not trypsin, cathepsin D or chym otrypsin resemble the post-mortem in situ degradation patterns, sugges ting a possible role for calpains in tau metabolism in vivo. Tan incor porated into PHFs was considerably more resistant to proteolysis by ca lpain which can help to explain the persistence of these structures in Alzheimer's disease.