Neurology, Neuroscience and Neuropharmacology

Biography

Biography: Ricardo B. Maccioni

Abstract

Alzheimer’s disease (AD) is a progressive neurodegenerative disease, characterized by behavioral disorders, loss of memory and cognitive impairment affecting more than 48 millions worldwide. Cumulative evidence shows that innate immunity participates in the pathogenesis of AD. According with our neuroimmunomodulation hypothesis, microglial activation modifies the cross-talks between microglia and neurons. Thus, glial activation by the so called “damaged signals” triggers a cascade of pathological events leading to hyperphosphorylation and oligomerization of the tau protein, associated with cognitive impairment. This activation depends on the type and intensity of the stimulus. In AD, a persistently active microglial condition could generate neuronal damage and neurodegeneration favored by ApoE4, causing the release of pathological tau toward the extraneuronal environment. Released tau would subsequently cause reactivation of microglial cells, thus promoting a positive feedback and generating a continuous cell damage. However, from the pathophysiological point of view, AD is significantly more complex that just inducing a loss of memory. As initial events in the pathogenesis of this neurodegenerative disease, alterations in the dopaminergic pathway together with serotonin depletion in the elderly lead to late onset depression according with recent evidences. These events seem to occur together with immunomodulatory alterations that lead to tau oligomerization in the course of neurofibrillary tangles formation. Interestingly, mood disorders are followed by neuroinflammatory processes and structural/functional alterations that lead to cognitive impairment in the context of AD (supported by Innova Corfo and the ICC).