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.
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