IL-1β, IL-6, IL-10, and TNFα Single Nucleotide Polymorphisms in Human Influence the Susceptibility to Alzheimer's Disease Pathology.

Autor:	Babić Leko M; Department of Neuroscience, Croatian Institute for Brain Research, University of Zagreb Medical School, Zagreb, Croatia., Nikolac Perković M; Department of Molecular Medicine, Institute Ruđer Bošković, Zagreb, Croatia., Klepac N; Department of Neurology, University Hospital Centre Zagreb, Zagreb, Croatia., Štrac DŠ; Department of Molecular Medicine, Institute Ruđer Bošković, Zagreb, Croatia., Borovečki F; Department of Neurology, University Hospital Centre Zagreb, Zagreb, Croatia., Pivac N; Department of Molecular Medicine, Institute Ruđer Bošković, Zagreb, Croatia., Hof PR; Nash Family Department of Neuroscience, Friedman Brain Institute, and Ronald M. Loeb Center for Alzheimer's Disease, Icahn School of Medicine at Mount Sinai, New York, NY, USA., Šimić G; Department of Neuroscience, Croatian Institute for Brain Research, University of Zagreb Medical School, Zagreb, Croatia.
Jazyk:	angličtina
Zdroj:	Journal of Alzheimer's disease : JAD [J Alzheimers Dis] 2020; Vol. 75 (3), pp. 1029-1047.
DOI:	10.3233/JAD-200056
Abstrakt:	Background: Neuroinflammation plays an important role in Alzheimer's disease (AD). During this process, activated microglia release pro-inflammatory cytokines such as interleukin (IL)-1α, IL-1β, IL-6, and tumor necrosis factor α (TNFα) that participate in neuron damage, but also anti-inflammatory cytokines (such as IL-10), which maintain homeostasis of immune response. Previous studies showed the association of IL-1α -889C/T (rs1800587), IL-1β-1473G/C (rs1143623), IL-6 -174C/G (rs1800795), IL-10 -1082G/A (rs1800896), and TNFα -308A/G (rs1800629) polymorphisms with AD. Objective: We aimed to investigate whether people with certain IL-1α, IL-1β, IL-6, IL-10, and TNFα genotypes in these polymorphisms are more prone to develop AD-related pathology, reflected by pathological levels of cerebrospinal fluid (CSF) AD biomarkers including amyloid-β1-42, total tau (t-tau), tau phosphorylated at Thr 181 (p-tau181), Ser 199 (p-tau199), and Thr 231 (p-tau231), and visinin-like protein 1 (VILIP-1). Methods: The study included 115 AD patients, 53 patients with mild cognitive impairment, and 11 healthy controls. The polymorphisms were determined using real-time polymerase chain reaction. Levels of CSF biomarkers were determined by enzyme-linked immunosorbent assay. Results: A significant increase in p-tau CSF levels was found in patients with the AA IL-10 -1082G/A and GG TNFα -308A/G genotypes, and in carriers of a G allele in IL-1β -1473C/G and IL-6 -174C/G polymorphisms. t-tau levels were increased in carriers of a G allele in IL-1β -1473C/G polymorphism. An increase in VILIP-1 levels was observed in patients with CG and GG IL-1β -1473C/G, GC IL-6 -174C/G, and GG TNFα -308A/G genotype. Conclusion: These results suggest that persons carrying certain genotypes in IL10 (-1082G/A), IL1β (1473C/G), IL6 (-174C/G), and TNFIα (-308A/G) could be more vulnerable to development of neuroinflammation, and consequently of AD.
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu