Aggregation-dependent interaction of the Alzheimer's beta-amyloid and microglia

Chronic glial activation possibly plays a role in chronic neurodegeneration in Alzheimer's disease (AD). It has been shown that amyloid peptide is cap able of activating microglial cells in vitro. The aim of this study was to further characterize the structural preconditions for amyloid peptide in or der to activate glial cells and to investigate whether this peptide is also able to induce glial activation in the living brain. We observed that amyloid peptide induced strong cellular activation in prim ary microglial cell culture as detected by the release of stable metabolite s of nitric oxide (NO), when the peptide was fibrillar. For this activation , co-stimulation with interferon-gamma was a precondition. Using microdialy sis of the living brain in a rat we observed pronounced NO generation when fibrillar amyloid peptide was stereotaxically injected. Non-fibrillar amylo id peptide did not induce such a glial reaction. No administration of inter feron-gamma or any other co-stimulatory factor was necessary in vivo. Thus, we show that fibrillar, but not non-fibrillar amyloid peptide induced glial activation also in vivo. In the case of the living brain, the presen ce of deposits of fibrillar amyloid peptide could maintain a chronic microg lial activation, ultimately leading to the progressive neurodegeneration as sociated with Alzheimer's disease.