Protein phosphatase 2A (PP2A) is the predominant serine/threonine phosphatase in eukaryotic cells. In the brains of patients with Alzheimer’s disease (AD), decreased PP2A activities were observed, which is suggested to be involved in neuro.brillary tangle (NFT) formation, disturbed amyloid precursor protein (APP) secretion and neurodegeneration in AD brain. 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 underlie PP2A inactivation in AD. β-amyloid (Aβ) overproduction, estrogen deficiency and impaired homocysteine metabolism are the possible up-stream factors that inactivate PP2A in AD neurons. Further studies are required to disclose the role of PP2A in Alzheimer’s disease.