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P3–271: Expression of interleukin 18 is increased in the brain of Alzheimer's disease patients
Author(s) -
Ojala Johanna,
Alafuzoff Irina,
Herukka Sanna-Kaisa,
Pirttilä Tuula
Publication year - 2006
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2006.05.1540
Subject(s) - neocortex , microglia , atrophy , hippocampus , western blot , interleukin , cytokine , pathology , endocrinology , biology , medicine , chemistry , neuroscience , inflammation , biochemistry , gene
Background: Characteristic features in Alzheimer’s disease (AD) brains are cortical atrophy, loss of neurons, mainly of amyloid(A ) composed plaques (P), and hyperphosphorylated tau containing neurofibrillary tangles in the hippocampus and in various regions of the neocortex. Both astrocytes and microglia are found in association with the Ps. The activation of microglia e.g. by A or microbes results in production of inflammatory cytokines, which can lead to nerve cell destruction. Interleukin 18 (IL-18, interferon-inducing factor, IL-1 ) is an inflammatory cytokine, which shares structural similarities with the IL-1 family of proteins and activities with IL-12. Similarly to IL-1 , it is cleaved by caspase-1 (ICE) to an active secreted form. Objectives: Our goal is to find new potential AD-pathology associated biomarkers and possible targets for therapeutics. Methods: We examined RNA (array) and protein expression (Western blot) in the frontal cortex of the AD patients. The non-demented age matched controls showed no Ps. The post-mortem time varied from 3-12 h. Results: Expression of IL-18 RNA was increased in the frontal regions in AD brains as compared to the control brains (AD: mean 5.37, SD 4.05, n 6; control: mean 0.62, SD 0.33, n 3, p 0.02). Also the levels of ICE and IL-1 RNA showed an increase in AD (ICE: AD mean 1.65, SD 0.53, n 6, control 0.55, SD 0.38, n 3; IL-1 : AD mean 5.34, SD 2.88, n 6; control mean 3.35, SD 4.66, n 2). The protein levels of IL-18 and IL-1 precursor showed a significant increase in AD brains as well (IL-18: AD mean 6.74, SD 3.05, n 14; control mean 1.49, SD 0.58, n 5; p 0.001; IL-1 precursor: AD mean 6.94, SD 3.01, n 14; control mean 3.42, SD 3.57, n 5; p 0.05). Moreover, the levels of ICE protein tended to be higher in AD than in the control brains but the difference did not reach statistical significance (AD: mean 5.71, SD 5.26, n 14; control: mean 3.64, SD 4.37, n 5). Protein levels of IL-18 and IL-1 correlated with A load but not with the number of NFTs tau. Conclusions: A may induce the synthesis of IL-18 as a part of the amyloid-associated inflammatory reaction.