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 pathogene sis of Alzheimer's disease is supported by the growing evidence that inflam matory proteins, which are produced by reactive astrocytes, promote the tra nsformation of diffuse P-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-l which triggers, secondaril y, the crucial activation of astrocytes. Reactive functional changes of gli al cells seem to be controlled by an altered balance of the second messenge rs Ca2+ and cAMP and can be counterregulated by the endogenous cell modulat or adenosine which strenghtens the cAMP-dependent signalling chain. A furth er reinforcement of the homeostatic adenosine effects on glial cells by pha rmaca, such as propentofylline, may add to neuroprotection in Alzheimer's d isease.