The neuropathology associated with Alzheimer's disease (AD) is characterized by the presence of extracellularly neuritic plaques, intracellularly neurofibrillary tangles and the loss of basal forebrain cholinergic neurons. The neuritic plaque is composed of a core of amyloid-beta peptide (Abeta) while the neurofibrillary tangles contain phosphorylated tau protein, and, as such, both Abeta and tau are important molecules associated with AD. In healthy human bodies, clearance mechanisms for Abeta are available; yet if clearance fails, Abeta accumulates, increasing the risk of neurotoxicity in the brain. Tau, one of the main microtubule-associated proteins, will be hyperphosphorylated and lose the ability to bind microtubules when the homeostasis of phosphorylation and dephosphorylation is disturbed in neurons. Accumulated Abeta and hyperphosphorylated tau are thought to be coexistent. Research on the pathological changes in AD indicates that accumulated Abeta in vivo may initiate the hyperphosphorylation of tau. Also, the signal transduction pathways of tau hyperphosphorylation may be related to accumulated Abeta. In this review, we will discuss how Abeta accumulates, how tau protein is hyperphosphorylated, and how accumulated Abeta initiates hyperphosphorylation of tau protein in AD.