During the past few years, an increasing set of evidence has supported the major role of deregulation of the interaction patterns between glial cells and neurons in the pathway toward neuronal degeneration. Neurons and glial cells, together with brain vessels, constitute an integrated system for brain function. Inflammation is a process related with the onset of several neurodegenerative disorders, including Alzheimer's disease (AD). Several hypotheses have been postulated to explain the pathogenesis of AD, but none provides insight into the early events that trigger metabolic and cellular alterations in neuronal degeneration. The amyloid hypothesis was sustained on the basis that Abeta-peptide deposition into senile plaques is responsible for neurodegeneration. However, recent findings point to Abeta oligomers as responsible for synaptic impairment in neuronal degeneration. Amyloid is only one among many other major factors affecting the quality of neuronal cells. Another explanation derives from the tau hypothesis, supported by the observations that tau hyperphosphorylations constitute a common feature of most of the altered signaling pathways in degenerating neurons. Altered tau patterns have been detected in the cerebrospinal fluids of AD patients, and a close correlation was observed between the levels of hyperphosphorylated tau isoforms and the degree of cognitive impairment. On the other hand, the anomalous effects of cytokines and trophic factors share in common the activation of tau hyperphosphorylation patterns. In this context, a neuroimmunological approach to AD becomes relevant. When glial cells that normally provide neurotrophic factors essential for neurogenesis are activated by a set of stressing events, they overproduce cytokines and NGF, thus triggering altered signaling patterns in the etiopathogenesis of AD. A solid set of discoveries has strengthened the idea that altered patterns in the glia-neuron interactions constitute early molecular events within the cascade of cellular signals that lead to neurodegeneration in AD. A direct correlation has been established between the Abeta-induced neurodegeneration and cytokine production and its subsequent release. In effect, neuroinflammation is responsible for an abnormal secretion of proinflammatory cytokines that trigger signaling pathways that activate brain tau hyperphosphorylation in residues that are not modified under normal physiological conditions. Other cytokines such as IL-3 and TNF-alpha seem to display neuroprotective activities. Elucidation of the events that control the transitions from neuroprotection to neurodegeneration should be a critical point toward elucidation of AD pathogenesis.