Expression of interleukin-18 is increased in the brains of Alzheimer's disease patients.
The inflammatory cytokines can initiate nerve cell degeneration and enhance the plaque production typically found in Alzheimer's disease (AD). Interleukin-18 (IL-18) is an inflammatory cytokine, which can induce the expression of interferon-gamma. This interleukin shares similarities with the IL-1 family of proteins. Like IL-1 beta, IL-18 is cleaved by caspase-1 (ICE) to an active secreted form. We examined the expressions of IL-18, -1 beta and ICE in different brain regions from AD patients that were categorized with respect to the Braak stage, and age-matched with non-demented controls. The levels of total-RNA and protein of IL-18 and ICE were increased, especially in the frontal lobe of AD patients and this change was not modified by ApoE genotype. Immunohistochemistry of AD brain samples detected IL-18 in microglia, astrocytes, and surprisingly in neurons, and it is also co-localized not only with amyloid-beta plaques but also with tau. In CSF, elevated IL-18 level was detected only in men and it also correlated with CSF tau in MCI. IL-18 may thus be a potential biomarker for men. Plasma levels of IL-18 showed no correlation with the disease. In conclusion, amyloid-beta may induce the synthesis of IL-18, and IL-18 kinases involved in tau phosphorylation as a part of the amyloid-associated inflammatory reaction.
Department of Neuroscience and Neurology, University of Kuopio, Canthia, P.O. Box 1627, FIN-70211 Kuopio, Finland. Johanna.Ojala@uku.fi
Johanna
J
Ojala
Irina
I
Alafuzoff
Sanna-Kaisa
SK
Herukka
Thomas
T
van Groen
Heikki
H
Tanila
Tuula
T
Pirttilä
D000544:Alzheimer Disease / Q000378:metabolism*; D001921:Brain / Q000378:metabolism*; D020170:Caspase 1 / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism*; D006801:Humans; D020382:Interleukin-18 / Q000378:metabolism*; D015854:Up-Regulation
D016207:Cytokines; D020382:Interleukin-18; D020170:Caspase 1