Homocysteine induces τ hyperphosphorylation in rats

Epidemiological and clinical data suggest that homocysteine (Hcy) may increase the risk of Alzheimer's disease, but the underlying mechanisms are elusive. To investigate the effect of Hcy on phosphorylation of tau, we injected Hcy into the lateral cerebral ventricle of rats. We found that level of the hyperphosphorylated tau at PHF-I (Ser396/404) and tau-l (Ser198/199/202) epitopes was elevated prominently at 6, 9, and 12h after the injection, and it was recovered to normal at 24h. Simultaneously, the level of protein phosphatase-2A catalytic subunit (PP-2Ac) was reduced markedly as compared with control. These results imply that Hcy may induce hyperphosphorylation of 7 with PP-2Ac involved mechanism.