engleski

IL-1β single nucleotide polymorphism as potential genetic biomarker of Alzheimer's disease

Neuroinflammation commences years before Alzheimer's disease (AD). Its association with both amyloid and tau pathology is well documented. Activated microglia in the AD brain release pro- inflammatory cytokines that can damage neurons, while anti-inflammatory cytokines are also released to oppose this process. Association of IL-1β -1473C/G polymorphisms with AD was not previously documented. In this study we assessed whether people carrying certain genotype in this polymorphism have higher risk for AD. We tested the levels of cerebrospinal fluid (CSF) biomarkers, event-related potentials (ERP), and various neuropsychological tests between patients with different IL-1β -1473 genotype. After blood collection, isolation of DNA, and determination of polymorphisms, 157 subjects were tested neuropsychologically, including AD patients, mild cognitive impairment (MCI) patients, patients with other causes of dementia, and healthy controls. ERP were measured by electroencephalography (EEG) in cohort of 54 patients, while CSF biomarkers (amyloid β1-42 [Aβ1-42], total tau, phosphorylated tau proteins (at epitopes 181, 199 and 231) and visinin-like protein 1 [VILIP-1]) were measured by enzyme-linked immunosorbent assay (ELISA) in the group of 179 patients. A significant increase in total tau, p-tau199, p-tau231 and VILIP-1 CSF levels was found in carriers of a G allele in IL- 1β –1473C/G polymorphism. Also, P300 latency was significantly prolonged in patients carrying the G allele in the IL-1β -1473 polymorphism and carriers of G allele showed worse performance on various neuropsychological tests (Alzheimer’s disease assessment scale-Cog, California Verbal Learning Test, Clock drawing test, and modified Mini‐Mental State Examination [MMSE corrected for age and education]). In conclusion, IL-1β -1473 polymorphism may represent a strong genetic biomarker of AD since persons carrying G allele in this polymorphism could be more vulnerable to development of neuroinflammation, and consequently of AD.

Alzheimer's disease ; biomarkers ; cerebrospinal fluid ; cytokines ; event-related potentials ; mild cognitive impairment ; Mini-Mental State Examination ; neuroflammation ; genetic polymorphisms

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