La neuroinfamacín como factor detonante del desarrollo de la enfermedad de Alzheimer

Abstract

The progressive increase in life expectancy of the world population has fostered a major concern in order to fnd effective avenues for diagnosis of treatment of Alzheimés disease (AD). Even tough AD pathogenesis is still unclear, new advances have allowed to understand that exposure of individuals to a series of environmental risk factors, named to as damage signals, play a main role in triggering the disease. This is important for AD prevention but also for the search of new treatment approaches. Activation of innate immunity in the central nervous system (CNS), essentially microglial cells, appears to be a key element in the neurodegenerative pathway. As a matter of fact, when microglia cells are exposed continuously to damage signals such as metabolites from conditions of hyperlipidemia, hyperglycemia, oxidative stress, head injury and trauma, recurrent infections, in addition to supramolecular aggregates such as tau flaments or b-amyloid oligomers, among other anomalous protein flaments, they respond by triggering the infammatory cascade. On this basis, we have postulated the neuroimmunomodulation hypothesis for Alzheimer's Disease. Therefore, we postulates that a long-term activation of brain innate immunity by a converging set of damage signals constitue a unifying mechanism that triggers the infammatory cascade, thus leading to irreversible alteration in the neuronal cytoskeleton. These concerted alterations in signaling mechanisms will lead in neuronal cells to a fnal common pathway, tau hyperphosphorylations, with the consequent self-aggregation of modifed tau and formation of paired helical flaments (PHFs), as the main triggering event for neurodegenration in AD.