The last neuronal division: a unifying hypothesis for the pathogenesis of Alzheimer's disease

Alzheimer's disease is the third biggest killer in the developed world after cancer and heart disease. Although the first description dates back to almost a century ago, we still do not understand the cellular-molecular mechanisms that lead to the development of the brain pathology. There is no efficient treatment for the patients. And even the symptomatic relief comes too late, because there is no diagnostic method that could identify patients before severe clinical symptoms develop. Almost every aspect of Alzheimer's research, whether on pathogenesis, diagnosis, risk factors or treatment strategies, seem to spark controversy nowadays. Studies that apparently contradict one another or propose alternate explanations are published monthly. Patients' hopes are raised with the announcement of each new drug trial. Then hope is lost when the trials fail. Ironically, while progressive research is hampered by apparent contradictions and lack of funding, the old dogmas survive in the textbooks and no real progress is made in terms of therapy. The purpose of this review is to take stock of the most discussed and most strongly opposing views on the pathogenesis of Alzheimer's disease. These views shape the Alzheimer field currently and some will hopefully one day shape the diagnostic and therapeutic approaches to the disease.