Alzheimer's disease and Aβ toxicity: from top to bottom

Evidence implicating the β-amyloid protein (Aβ) in the pathogenesis of Alzheimer's disease has steadily accumulated. However, the mechanism by which Aβ causes dementia is unknown. Here we argue that a more integrated, top–down approach to brain function is needed to assess the role of Aβ in Alzheimer's disease, and that more attention should be paid to the effects of Aβ on synaptic function rather than on cell death.