Protein phosphatase 2A (PP2A) is the predominant serine/threonine phosphatase in eukaryotic cells. In Alzheimer's disease (AD), PP2A activity is decreased. Decreased PP2A activity is suggested to be involved in NFT formation and neurodegeneration. PP2A is also involved in APP secreting pathway, thus probably participating the Abeta production. Based on our research and other previous findings, decreased PP2Ac level, decreased PP2A holoenzyme composition, increased level of PP2A inhibitors, increased PP2Ac Leu309 demethylation and Tyr307 phosphorylation could partly explain the mechanisms of PP2A inactivation in AD. Abeta over-production, estrogen deficiency and impaired homocysteine metabolism are the possible up-stream factors that inactivate PP2A in AD neurons. Further studies are needed to disclose the role of PP2A in Alzheimer's disease.