IL-1β, IL-6, IL-10, and TNFα Single Nucleotide Polymorphisms in Human Influence the Susceptibility to Alzheimer’s Disease Pathology
| Autor: | Nela Pivac, Goran Šimić, Mirjana Babić Leko, Matea Nikolac Perkovic, Patrick R. Hof, Fran Borovečki, Nataša Klepac, Dubravka Švob Štrac |
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| Rok vydání: | 2020 |
| Předmět: |
Male
0301 basic medicine Pathology Interleukin-1beta 0302 clinical medicine Genotype TNFα biology General Neuroscience Interleukin General Medicine Middle Aged Interleukin-10 Psychiatry and Mental health Clinical Psychology Interleukin 10 IL-10 Encephalitis Female Tumor necrosis factor alpha medicine.symptom Alzheimer’s disease medicine.medical_specialty tau Proteins Inflammation Single-nucleotide polymorphism Polymorphism Single Nucleotide 03 medical and health sciences Alzheimer's disease biomarkers IL-1 IL-6 inflammation polymorphisms TNFalpha Alzheimer Disease medicine Humans Genetic Predisposition to Disease Interleukin 6 Neuroinflammation Aged Amyloid beta-Peptides Interleukin-6 Tumor Necrosis Factor-alpha business.industry 030104 developmental biology biology.protein Geriatrics and Gerontology business 030217 neurology & neurosurgery |
| Zdroj: | Journal of Alzheimer's Disease. 75:1029-1047 |
| ISSN: | 1875-8908 1387-2877 |
| DOI: | 10.3233/jad-200056 |
| Popis: | 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: | OpenAIRE |
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