Figure 2.

The “Glial Cell Dysregulation Hypothesis” for Alzheimer’s disease (AD). The glial cell dysregulation hypothesis proposes that AD has its cause on changes on the activation and impaired regulation of microglia, which become increasingly cytotoxic decreasing their protective functions. Microglia is under the regulation of astrocytes which, among other factors, secrete TGFβ. Inflammatory activation, secondary to aging and to certain forms of pathological stimuli, can result in glial cell dysregulation. Dysregulated glia, though the abnormal release of cytokines, reactive species, and other mediators, contributes to the increased expression of Aβ precursor protein (APP) and aggregation of Aβ, as well to functional and degenerative changes of neurons, perpetuating abnormal activation of glia, synaptic dysfunction and cell damage.