Hypothesis on the pathogenesis of Alzheimer’s disease with special reference to amyloid β protein

Akira Tamaoka

Department of Neurology, Division of Clinical Medicine, Faculty of Medicine, University of Tsukuba

Amyloid β protein (Aβ) deposition in senile plaques was earlier considered to bigin the pathological cascade of Alzheimer’s disease (AD), suggesting that the aggregation of soluble Aβ monomer into insoluble Aβ fibrils plays an important role in its neurotoxicity. However, the concentrations of Aβ 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 Aβ oligomers, playing a more important role in the etiology of AD than insoluble Aβ fibrils (‘Aβ oligomer hypothesis’).

Address correspondence to Dr. Akira Tamaoka, Department of Neurology, Division of Clinical Medicine, Faculty of Medicine, University of Tsukuba (Tennoudai 1-1-1, Tsukuba, Ibaraki 305-8575, Japan)