title: Increased expression of interleukin-18 receptor in blood cells of subjects with mild cognitive impairment and Alzheimer's disease.
abstract: Inflammation has been proposed as a leading force in neurodegeneration and Interleukin (IL)-18 is a pro-inflammatory cytokine which is suggested to be implicated in Alzheimer's disease (AD). However, the meaning of the IL-18 participation in this disease is still unclear. Since IL-18 activity is mediated by its heterodimeric receptor complex IL-18Rα/β, we evaluated the presence of both IL-18R chains on peripheral blood cells of AD patients, as well as in individuals with Mild Cognitive Impairment (MCI), at increased risk to develop AD. More specifically, we compared the levels of CD14(+) monocytes and CD3(+) T-lymphocytes bearing IL-18Rα and β chains in the two groups of patients with those in healthy control subjects, both before and after in vitro cell treatment with lipopolysaccharide (LPS). While no differences in the levels of monocytes and T-lymphocytes bearing IL-18Rα chain were found among the three groups, either in untreated and LPS-treated conditions, the IL-18Rβ chain expression appeared differently regulated in MCI and AD patients, as compared to controls. In particular, the amount of IL-18Rβ-bearing monocytes was similar among the three groups at unstimulated conditions, while after LPS treatment it was increased in MCI vs. controls. A significant increase of IL-18Rβ-bearing T-lymphocytes was also observed in MCI and AD vs. controls, both in untreated and LPS-stimulated conditions. Our findings indicate that the expression of IL-18R complex on blood cells is perturbed in AD and even more markedly in its preclinical state of MCI, confirming that an increased peripheral activity of IL-18 may be involved in the early phase of AD pathophysiology.
authors.affiliation: Department of Clinical and Behavioral Neurology, IRCCS Santa Lucia Foundation, Via Ardeatina 306, I-00179 Rome, Italy. f.salani@hsantalucia.it
authors.forename: Francesca
authors.initials: F
authors.lastname: Salani
authors.forename: Antonio
authors.initials: A
authors.lastname: Ciaramella
authors.forename: Federica
authors.initials: F
authors.lastname: Bizzoni
authors.forename: Francesca
authors.initials: F
authors.lastname: Assogna
authors.forename: Carlo
authors.initials: C
authors.lastname: Caltagirone
authors.forename: Gianfranco
authors.initials: G
authors.lastname: Spalletta
authors.forename: Paola
authors.initials: P
authors.lastname: Bossù
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000097:blood*; D001773:Blood Cells / Q000378:metabolism*; D016022:Case-Control Studies; D060825:Cognitive Dysfunction / Q000097:blood*; D005260:Female; D006801:Humans; D053727:Interleukin-18 Receptor alpha Subunit / Q000097:blood*; D053728:Interleukin-18 Receptor beta Subunit / Q000097:blood; D008297:Male
chemical_list: C508572:IL18R1 protein, human; D053727:Interleukin-18 Receptor alpha Subunit; D053728:Interleukin-18 Receptor beta Subunit