Effects of immunomodulatory substances on phagocytosis of abeta(1-42) by human microglia

• Glial activation and increased inflammation characterize neuropathology in Alzheimer's disease (AD). The aim was to develop a model for studying phagocytosis of -amyloid (A) peptide by human microglia and to test effects thereupon by immunomodulatory substances. Human CHME3 microglia showed intracellular A colocalized with lysosome-associated membrane protein-2, indicating phagocytosis. This was increased by interferon-, and to a lesser degree with Protollin, a proteosome-based adjuvant. Secretion of brain-derived neurotrophic factor (BDNF) was decreased by A and by interferon- and interleukin-1. These cytokines, but not A, stimulated interleukin-6 release. Microglia which phagocytosed A exhibited a higher degree of expression of interleukin-1 receptor type I and inducible nitric oxide synthase. In conclusion, we show that human microglia are able to phagocytose A and that this is associated with expression of inflammatory markers. A and interferon- decreased BDNF secretion suggesting a new neuropathological role for A and the inflammation accompanying AD.

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