Effects of Immunomodulatory Substances on Phagocytosis of Aβ (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 β-amyloid (Aβ) peptide by human microglia and to test effects thereupon by immunomodulatory substances. Human CHME3 microglia showed intracellular Aβ (1–42) colocalized with lysosome-associated membrane protein-2, indicating phagocytosis. This was increased by interferon-γ, and to a lesser degree with Protollin, a proteosome-based adjuvant. Secretion of brain-derived neurotrophic factor (BDNF) was decreased by Aβ (1–42) and by interferon-γ and interleukin-1β. These cytokines, but not Aβ (1–42), stimulated interleukin-6 release. Microglia which phagocytosed Aβ (1–42) 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 Aβ (1–42) and that this is associated with expression of inflammatory markers. Aβ (1–42) and interferon-γ decreased BDNF secretion suggesting a new neuropathological role for Aβ (1–42) and the inflammation accompanying AD.