Amyloid-beta-induced chemokine production in primary human macrophages and astrocytes.

In Alzheimer's disease (AD), chemotaxis might be responsible for attracting glial cells towards the neuritic plaque. Using primary monocyte-derived macrophages and primary adult astrocytes as a model, amyloid-beta (Abeta) (1-42) was able to stimulate the production, as measured by RT-PCR, of MIP-1alpha and MIP-1beta mRNA in macrophages and MCP-1 in astrocytes. Cocultures showed in unstimulated as well as in Abeta-stimulated cells an increase in MIP-1alpha, MIP-1beta and MCP-1 mRNA.

Activation of human macrophages by amyloid-beta is attenuated by astrocytes.

In Alzheimer's disease, neuritic amyloid-beta plaques along with surrounding activated microglia and astrocytes are thought to play an important role in the inflammatory events leading to neurodegeneration. Studies have indicated that amyloid-beta can be directly neurotoxic by activating these glial cells to produce oxygen radicals and proinflammatory cytokines. This report shows that, using primary human monocyte-derived macrophages as model cells for microglia, amyloid-beta(1-42) stimulate these macrophages to the production of superoxide anions and TNF-alpha.