Lifespan brain activity, β-amyloid, and Alzheimer's disease

Alzheimer's disease (AD) is the most common cause of progressive cognitive decline and dementia in adults. While the amyloid cascade hypothesis of AD posits an initiating role for the beta-amyloid (A beta) protein, there is limited understanding of why A beta is deposited. A growing body of evidence based on in vitro, animal studies and human imaging work suggests that synaptic activity increases A beta, which is deposited preferentially in multi-modal brain regions that show continuous levels of heightened activation and plasticity across the lifespan. Imaging studies of people with genetic predispositions to AD are consistent with these findings, suggesting a mechanism whereby neural efficiency or cognitive reserve may diminish A beta deposition. The aggregated findings unify observations from cellular and molecular studies with human cognitive neuroscience to reveal potential mechanisms of AD development.