The biochemical study on the etiology of Alzheimer's disease.

Alzheimer's disease has been characterized by senile plaque and neurofibrillary tangle in the brain. However, their relation to etiology of this disease has been left unclear. Recently it has been clarified that neurofibrillary tangle consists of highly phosphorylated tau protein. Then we have started to identify the enzyme(s) responsible for this phosphorylation and obtained tau protein kinase I and II. Tau protein kinase I phosphorylated not only tau protein but also pyruvate dehydrogenase, phosphorylation of which caused inactivation of this enzyme and finally led the cell to death. Then we have proved that TPKI is upregulated in AD brain but not in control brain. Upregulation of TPKI was induced by treating the neuronal cells with Abeta protein. Finally we have identified oligomeric aggregation of Abeta protein named Amylospheroid is highly potent to degenerate neuronal cells both in vitro and in vivo systems.