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

the progressive increase in life expectancy of the world population has fostered a major concern in order to find effective avenues for diagnosis of treatment of alzheimer's 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 filaments or b-amyloid oligomers, among other anomalous protein filaments, they respond by triggering the inflammatory 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 constitute a unifying mechanism that triggers the inflammatory cascade, thus leading to irreversible alteration in the neuronal cytoskeleton. these concerted alterations in signaling mechanisms will lead in neuronal cells to a final common pathway, tau hyperphosphorylations, with the consequent self-aggregation of modified tau and formation of paired helical filaments (phfs), as the main triggering event for neurodegenration in ad.