Neurobiology of Aging 30 (2009) 198–209 Expression of interleukin-18 is increased in the brains of Alzheimer’s disease patients Johanna Ojala a,b,∗ , Irina Alafuzoff a,c,1 , Sanna-Kaisa Herukka a,2 , Thomas van Groen a,f,3 , Heikki Tanila e,4 , Tuula Pirttil¨ a a,d,5 a Department of Neuroscience and Neurology, University of Kuopio, Canthia, P.O. Box 1627, FIN-70211 Kuopio, Finland b Clinical Research Centre/Brain Research Unit, University of Kuopio, Mediteknia, P.O. Box 1627, FIN-70211 Kuopio, Finland c Department of Pathology and Forensic Medicine, University of Kuopio, University Hospital, FIN-70200 Kuopio, Finland d University of Kuopio, University Hospital, Neurology (Bldg. 5), P.O. Box 1777, FIN-70211 Kuopio, Finland e Department of Neurobiology, A.I. Virtanen Institute for Molecular Sciences, BioTeknia, Neulaniementie 2, FIN-70210 Kuopio, Finland f Department of Cell Biology, University of Alabama at Birmingham, THT 912, 1900 University Boulevard, Birmingham, AL 35294-0006, USA Received 26 May 2006; received in revised form 8 June 2007; accepted 8 June 2007 Available online 20 July 2007 Abstract 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-. This interleukin shares similarities with the IL-1 family of proteins. Like IL-1, IL-18 is cleaved by caspase-1 (ICE) to an active secreted form. We examined the expressions of IL-18, -1 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- 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- may induce the synthesis of IL-18, and IL-18 kinases involved in tau phosphorylation as a part of the amyloid-associated inﬂammatory reaction. © 2007 Elsevier Inc. All rights reserved. Keywords: Interleukin-18; Cytokine; Caspase-1; Inﬂammation; Alzheimer’s disease; SAMP8; APP(Swe/PS(A246E) mouse ∗ Corresponding author at: Clinical Research Centre/Brain Research Unit, University of Kuopio, Mediteknia, P.O. Box 1627, FIN-70211 Kuopio, Fin- land. Tel.: +358 17 163540; fax: +358 17 163539. E-mail addresses: Johanna.Ojala@uku.ﬁ (J. Ojala), Irina.Alafuzoff@uku.ﬁ (I. Alafuzoff), Sanna-Kaisa.Herukka@uku.ﬁ (S.-K. Herukka), vangroen@uab.edu (T. van Groen), Heikki.Tanila@uku.ﬁ (H. Tanila), Tuula.Pirttila@uku.ﬁ (T. Pirttil¨ a). 1 Tel.: +358 17 173471; fax +358 17 162753. 2 Tel.: +358 17 163213; fax: +358 17 162048. 3 Tel.: +1 205 934 5940; fax: +1 205 934 7029. 4 Tel.: +358 17 162084; fax: +358 17 163030. 5 Tel.: +358 17 173029; fax: +358 17 173019. 1. Introduction Alzheimer’s disease (AD) is a neurodegenerative disor- der characterized by the accumulation of amyloid- (A) protein in the brain parenchyma as well as in the walls of leptomeningeal and parenchymal vessels. In addition, neu- roﬁbrillary changes and extensive neuronal loss are seen. The neuritic plaques and neuroﬁbrillary tangles (NFTs) are considered to be hallmark lesions of the disease (Braak and Braak, 1991; Khachaturian, 1985; Mirra et al., 1991). 0197-4580/$ – see front matter © 2007 Elsevier Inc. All rights reserved. doi:10.1016/j.neurobiolaging.2007.06.006