Developing preventive therapies for chronic diseases: lessons learned from Alzheimer's disease

A remarkable rise in life expectancy during the past century has made Alzheimer's disease (AD) the most common form of progressive intellectual failure in humans. Patients with AD lose their most human qualities-reasoning, abstraction, language, and memory. The brain plaques that Alois Alzheimer first described 100 years ago have inspired the search for genetic alterations that underlie AD. Four genes have been unequivocally implicated to date in inherited forms of AD, where mutations or natural variations in these genes cause excessive accumulation of the amyloid beta-protein, the building block of amyloid plaques. This aggregation leads to subsequent neuronal degeneration in brain regions important for memory and cognition. The discovery of the genes involved in the mechanisms of amyloid beta-protein build-up in AD, coupled with cell culture and animal models of their involved pathways, has led to the development of specific pharmacological strategies to lower amyloid beta-protein levels as a way of treating or preventing all forms of the disease. While hard work lies ahead, the movement from basic research to the clinic in AD represents a triumph of reductionist biology applied to the most complex of all biological systems, the human cerebral cortex.