Pathological immuno-reactions of glial cells in Alzheimer's disease and possible sites of interference

A significant role of a pathological glial cell activation in the pathogenesis of Alzheimer's disease is supported by the growing evidence that inflammatory proteins, which are produced by reactive astrocytes, promote the transformation of diffuse β-amyloid deposits into the filamentous, neurotoxic form. A number of vicious circles, driven by the release of TNF-a and free oxygen radicals from microglial cells, may cause an upregulated microglial activation and their production of interleukin-1 which triggers, secondarily, the crucial activation of astrocytes. Reactive functional changes of glial cells seem to be controlled by an altered balance of the second messengers Ca2+ and cAMP and can be counter-regulated by the endogenous cell modulator adenosine which strengthens the cAMP-dependent signalling chain. A further reinforcement of the homeostatic adenosine effects on glial cells by pharmaca, such as propentofylline, may add to neuroprotection in Alzheimer's disease.