Alzheimer's disease 2012: the great amyloid gamble

Alzheimer's disease threatens to become the scourge of the 21st century. Hundreds of millions of aging people throughout the world are at risk, but it is clear that the disease encompasses more than just the natural aging process. Deposits of amyloid β peptides in the brains of demented individuals are a defining feature of the disease, yet two decades of intensive investigation, focusing on reducing or removing amyloid deposits, have failed to produce any meaningful therapeutic interventions. Some researchers question whether amyloid is the appropriate target. Others maintain that early, presymptomatic intervention would be a more informative test, and propose large-scale clinical trials in patients who are believed to be in the earliest, and potentially reversible, stages of the disease. This review explores the wisdom of that approach.