THE EXTENT OF PHOSPHORYLATION OF FETAL-TAU IS COMPARABLE TO THAT OF PHF-TAU FROM ALZHEIMER PAIRED HELICAL FILAMENTS

The relationship between Alzheimer's disease (AD) and expression of fe tal proteins was examined by: (i) determining the phosphate content of tau prepared from fetal brains (F-tau); (ii) comparing F-tau, tau fro m normal adult human brains (N-tau) and tau from paired helical filame nts in AD brains (PHF-tau) for phosphate content; and (iii) testing th e reactivity of F-tau with five antibodies known to recognize PHF-tau. The antibodies have been reported to recognize phosphate dependent ep itopes at the carboxy-terminal half of the tau molecule. Our data show s that on the average, F-tau contains 7 mol phosphate/mol protein, whi ch is comparable to the phosphate content of PHF-tau, but is 3-4 times higher than that of N-tau. Immunoblotting shows that all of the teste d antibodies reacted with F-tau on immunoblots, indicating that F-tau and PHF-tau are phosphorylated at similar sites. A difference between PHF-tau and F-tau is the state of phosphorylation in the Tau-I epitope , an epitope reactive with a monoclonal anti-tau antibody, Tau-1. This epitope, which is phosphorylated in all PHF-tau, is phosphorylated on ly in some of the F-tau. The sharing of phosphorylated sites between F -tau and PHF-tau has also been reported by others in studies with anti bodies to different and similar phosphorylated epitopes. Together thes e observations indicate that the extent and the site of phosphorylatio n in F-tau and PHF-tau tau are similar. Although hyperphosphorylation of tau proteins may be an important step for PHF formation, the absenc e of AD type pathology in fetal brains containing hyperphosphorylated tau suggests that the transformation of soluble forms of normal tau to AD type cytoskeletal abnormalities may require the presence of other factors.