Il-1 Beta, Il-6, Il-10, And Tnf Alpha Single Nucleotide Polymorphisms In Human Influence The Susceptibility To Alzheimer'S Disease Pathology

Background: Neuroinflammation plays an important role in Alzheimer's disease (AD). During this process, activated microglia release pro-inflammatory cytokines such as interleukin (IL)-1 alpha, IL-1 beta, IL-6, and tumor necrosis factor alpha (TNF alpha) 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-1 alpha -889C/T (rs1800587), IL-1 beta-1473G/C (rs1143623), IL-6 -174C/G (rs1800795), IL-10 -1082G/A (rs1800896), and TNF alpha-308A/G (rs1800629) polymorphisms with AD.Objective: We aimed to investigate whether people with certain IL-1 alpha, IL-1 beta, IL-6, IL-10, and TNF alpha genotypes in these polymorphisms are more prone to develop AD-related pathology, reflected by pathological levels of cerebrospinal fluid (CSF) AD biomarkers including amyloid-beta(1-42), total tau (t-tau), tau phosphorylated at Thr 181 (p-tau(181)), Ser 199 (p-tau(199)), and Thr 231 (p-tau(231)), 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 TNF alpha -308A/G genotypes, and in carriers of a G allele in IL-1 beta-1473C/G and IL-6 -174C/G polymorphisms. t-tau levels were increased in carriers of a G allele in IL-1 beta-1473C/G polymorphism. An increase in VILIP-1 levels was observed in patients with CG and GG IL-1 beta-1473C/G, GC IL-6 -174C/G, and GG TNF alpha-308A/G genotype.Conclusion: These results suggest that persons carrying certain genotypes in IL10 (-1082G/A), IL1 beta (1473C/G), IL6 (-174C/G), and TNFI alpha (-308A/G) could be more vulnerable to development of neuroinflammation, and consequently of AD.