The inverse association of cancer and Alzheimer's: a bioenergetic mechanism

Abstract

The sporadic forms of cancer and Alzheimer's disease (AD) are both age-related metabolic disorders. However, the molecular mechanisms underlying the two diseases are distinct: cancer is described by essentially limitless replicative potential, whereas neuronal death is a key feature of AD. Studies of the origin of both diseases indicate that their sporadic forms are the result of metabolic dysregulation, and a compensatory increase in energy transduction that is inversely related. In cancer, the compensatory metabolic effect is the upregulation of glycolysis—the Warburg effect; in AD, a bioenergetic model based on the interaction between astrocytes and neurons indicates that the compensatory metabolic alteration is the upregulation of oxidative phosphorylation—an inverse Warburg effect. These two modes of metabolic alteration could contribute to an inverse relation between the incidence of the two diseases. We invoke this bioenergetic mechanism to furnish a molecular basis for an epidemiological observation, namely the incidence of sporadic forms of cancer and AD is inversely related. We furthermore exploit the molecular mechanisms underlying the diseases to propose common therapeutic strategies for cancer and AD based on metabolic intervention.