Abnormalities of Phosphatase 2A (PP2A) for Diagnosis and Treatment of Alzheimer's Disease

摘要

This invention relates to methods of diagnosing Alzheimer's disease and methods of screening for compounds for the treatment or prevention of Alzheimer's disease. The methods are based upon newly discovered differences in protein phosphatase 2A (PP2A) function and related molecular events in Alzheimer's disease cells compared to control cells. In one embodiment, differences in basal PP2A gene expression in Alzheimer's cells are compared to controls. In another embodiment differences in PP2A protein and enzyme activity are compared in test and control cells. In another embodiment differences in response to substances that inhibit PP2A function are compared. Still another embodiment detects differences in the subcellular distribution of phosphorylated Erk1/2, a substrate of PP2A, in normal and Alzheimer's disease cells. The detection of Alzheimer's disease-specific differences in PP2A function and related events in peripheral tissues provides the basis for highly practical and efficient tests and diagnostic test kits for the early diagnosis of Alzheimer's disease, as well as providing a biochemical basis for identifying therapeutic targets for drug development.