Effects of Immunomodulatory Substances on Phagocytosis of Aβ1–42 by Human Microglia. (11th April 2010)

• Record Type: Journal Article
• Authors: Hjorth, Erik; Frenkel, Dan; Weiner, Howard; Schultzberg, Marianne
• Other Names: Greig Nigel H. Academic Editor.
• Is Part Of: International journal of alzheimer's disease. Volume 2010(2010)
• Publication Date: 2010-04-11
• Subjects: Alzheimer's disease -- Periodicals; 616.831005
• DOI: 10.4061/2010/798424
• Languages: English
• ISSNs: 2090-8024

Abstract

Abstract : Glial activation and increased inflammation characterize neuropathology in Alzheimer's disease (AD). The aim was to develop a model for studying phagocytosis ofβ -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.