For more than 25 years one idea has dominated scientific thinking about Alzheimer's disease: the amyloid cascade hypothesis. It holds that the disorder, which afflicts about one in 10 Americans age 65 or older, is caused by a buildup in the brain of abnormal amyloid-beta protein, which eventually destroys neurons and synapses, producing the tragic symptoms of dementia. There's plenty of evidence for this. First, the presence of sticky clumps or “plaques” containing amyloid is a classic hallmark of the disease (along with tangles of a protein called tau). It was what Alois Alzheimer saw in the autopsied brain of patient zero in 1906. Second, families with inherited defects in amyloid precursor protein (APP) or in genes encoding proteins that process APP are plagued by early-onset Alzheimer's. Third, mice genetically engineered to churn out excess amyloid tend to develop memory problems and do better when the amyloid pileup is stopped.