Understanding the cause of sporadic Alzheimer's disease

The increasing prevalence of Alzheimer's disease (AD) and a lack of effective prevention or disease-modifying therapies are global challenges with devastating personal, social and economic consequences. The amyloid (A) hypothesis posits that cerebral -amyloidosis is a critical early event in AD pathogenesis. However, failed clinical trials of A-centric drug candidates have called this hypothesis into question. Whereas we acknowledge that the A hypothesis is far from disproven, we here re-visit the links between A, tau and neurodegeneration. We review the genetics, epidemiology and pathology of sporadic AD and give an updated account of what is currently known about the molecular pathogenesis of the disease.