Alzheimer’s disease: a molecular mechanism, new hypotheses, and therapeutic strategies

Human diseases involving protein misfolding and aggregation have received increasing attention in recent years. Alzheimer's disease and other diseases associated with aging are sweeping the developed countries whose populations are rapidly aging. Recent progress has improved our knowledge about molecular and cellular pathogenesis of these diseases. For more than 20 years, multiple diseases such as Alzheimer's and Parkinson's diseases have been associated with accumulation of abnormal protein fibrils. These self-assembling fibrils, referred as "amyloid," have been considered the pathogenic molecules that cause cellular degeneration. Accumulation of fibrillar Abeta in plaques underlies the theory for Alzheimer's disease. Recent experiments have provided evidence that fibrils are not the only neurotoxins. Soluble oligomers and protofibrils play a crucial role in causing cellular dysfunction and death. These oligomers, the missing links in the original amyloid cascade hypothesis, have been incorporated into an updated amyloid cascade. Despite new information gained, there is no disease-modifying treatment. New insights into disease mechanisms and new therapeutic strategies give hope for change.