[The pathophysiology of Alzheimer's disease with special reference to "amyloid cascade hypothesis"].

The neuropathological characteristics of the Alzheimer's disease (AD) brain include senile plaques, neurofibrillary tangles and neuronal cell loss extensively recognized in brain cortices. Biochemical studies revealed that senile plaques and neuronfibrillary tangles are composed mainly of amyloid beta protein and highly phosphorylated tau protein, a microtubule-associated protein, respectively. Abeta deposition in senile plaques was previously considered to initiate the pathological cascade of Alzheimer's disease (AD), suggesting that the aggregation of Abeta in insoluble Abeta fibrils plays an important role in its neurotoxicity ('amyloid cascade hypothesis'). However, the concentrations of Abeta required for fibrillization are higher than its physiological concentrations. In addition, cognitive decline in AD patients is not correlated with the levels of senile plaque formation. Currently, AD is believed to begin with synaptic dysfunction caused by soluble Abeta oligomers, playing a more important role in the etiology of AD than insoluble Abeta ibrils ('oligomer hypothesis').