Effects of Immunomodulatory Substances on Phagocytosis of Aβ1–42 by Human Microglia

Abstract EN

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 Aβ1–42 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 Aβ1–42 and by interferon-γ and interleukin-1β.

These cytokines, but not Aβ1–42, stimulated interleukin-6 release.

Microglia which phagocytosed Aβ1–42 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 Aβ1–42 and that this is associated with expression of inflammatory markers.

Aβ1–42 and interferon-γ decreased BDNF secretion suggesting a new neuropathological role for Aβ1–42 and the inflammation accompanying AD.