M. I. Behrens, C. Lendon and C. M. Roe Pages 196 - 204 ( 9 )
Cancer and Alzheimers disease (AD) are two common disorders for which the final pathophysiological mechanism is not yet clearly defined. In a prospective longitudinal study we have previously shown an inverse association between AD and cancer, such that the rate of developing cancer in general with time was significantly slower in participants with AD, while participants with a history of cancer had a slower rate of developing AD. In cancer, cell regulation mechanisms are disrupted with augmentation of cell survival and/or proliferation, whereas conversely, AD is associated with increased neuronal death, either caused by, or concomitant with, beta amyloid (Aβ) and tau deposition. The possibility that perturbations of mechanisms involved in cell survival/death regulation could be involved in both disorders is discussed. Genetic polymorphisms, DNA methylation or other mechanisms that induce changes in activity of molecules with key roles in determining the decision to “repair and live”- or “die” could be involved in the pathogenesis of the two disorders. As examples, the role of p53, Pin1 and the Wnt signaling pathway are discussed as potential candidates that, speculatively, may explain inverse associations between AD and cancer.
Alzheimer, cancer, tumor suppressors, Pin1, Wnt signaling pathway
Departamento de Neurologia y Neurocirugia, Hospital Clinico Universidad de Chile, Santos Dumont 999, Santiago Chile and Clinica Alemana, Chile.