engleski

Serotonergic receptor type 2A and inflammatory cytokines gene polymorphisms in Alzheimer’s disease patients

Alzheimer’s disease (AD) is a progressive and incurable neurodegenerative disease that usually affects people in the aged population over 60 years, and it is considered to be a result of mutual interaction of genetic and environmental factors. The disease manifests itself in behavioural changes, progressive loss of memory and cognitive functions, as well as presence of psychotic symptoms such as hallucinations and delusions. Neuropathology of the disease is associated with a very characteristic aggregate of amyloid-β peptide plaques and neurofibrillary tangles of hyperphosphorylated tau protein in the brain, which leads to deterioration of neurons. The accumulation of plaques and tangles is accompanied by the development of inflammation and increased secretion of inflammatory mediators, such as IL-6, TNF-α and IL-10, trying to remove the pathological background. Because of their inefficiency, the inflammatory process becomes chronic and neurotoxic. In addition, the results of some studies indicate a decreased concentration of serotonin, as well as the loss of serotonin receptors type 2A, which suggests that these receptors might be associated with the pathogenesis of AD. The aim of this study was to a) determine the genotype distributions and allele frequencies of HRT2A, IL6, IL10, TNFA and APOE polymorphisms in AD patients and healthy elderly individuals, b) determine the same parameters for AD patients with and without psychotic symptoms and c) determine the possible synergistic effect between the polymorphisms. This is the first study to analyze the possible relationship between rs6314 polymorphism and AD, and between rs1800795 polymorphism and psychotic symptoms in AD. The results showed a lack of association between these polymorphisms and AD, while the analysis of psychotic symptoms associated with AD showed significant results only for rs6314 polymorphism between groups of male and female AD patients with psychotic symptoms (p = 0.05 for genotype distributions, p = 0.04 for allele frequency). Due to the lack of association with AD and statistical methods with power that could accurately determine the synergistic effects of polymorphisms, such analysis was not performed.

Alzheimer’s disease ; serotonin receptor type 2A ; inflammatory cytokines ; ApoE ; polymorphism ; real-time PCR

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