Alzheimer's disease as oligomeropathy

Alzheimer's disease (AD) is the most common age-related neurodegenerative disorder and is characterized by pathological aggregates of amyloid beta-protein (A beta) and tau protein. On the basis of genetic evidence, biochemical data, and animal models, A beta has been suggested to be responsible for the pathogenesis of AD (the amyloid hypothesis). A beta molecules tend to aggregate to form oligomers, protofibrils, and mature fibrils. Although mature fibrils in the final stage have been thought to be the cause of AD pathogenesis, recent studies using synthetic A beta peptides, a cell culture model, A beta precursor protein transgenic mice models, and human samples, such as cerebrospinal fluids and postmortem brains of AD patients, suggest that pre-fibrillar forms (oligomers of A beta) are more deleterious than are extracellular fibril forms. Based on this recent evidence showing that oligomers have a central role in the pathogenesis of AD, the term oligomeropathy could be used to define AD and other protein-misfolding diseases. In this review, I discuss recent developments in the oligomer hypothesis including our research findings regarding the pathogenesis of AD. (C) 2017 Elsevier Ltd. All rights reserved.