Role of the genetic polymorphism of inflammatory cytokines in patients with Alzheimer's disease.

Alzheimer’s disease (AD) is a dementia characterized by neuronal loss, atrophy, gliosis and clinically by progressive cognitive impairment. In the last years several experimental evidences both “in vitro” and “in vivo” have suggested a possible involvement of the immune system in the pathogenesis and/or in the progression of the disease. Considering the relative low quantity of studies about multiple cytokine gene polymorphisms in AD, we were prompted to studying the panel polymorphism of related cytokine genes in an AD group of patients and in a control healthy group. In a case control, using a unified method of genotyping (PCR–SSP methodology), we have examined 22 polymorphisms in 13 cytokine genes in 63 caucasian AD patients with medium–high level of dementia (Mini Mental State Examination MMSE <24) and 65 normal controls belonging to the same ethnic group matched by age and gender affected by non inflammatory neuropsychiatric diseases. The patients and the control group did not shown any symptoms or signs of inflammatory process. Polymorphisms in the genes for IL-1A, IL-1β, IL-2, IL-4, IL-6, IL-10, IL-12, IFN-γ, TGF-β, TNF-α and for the cytokine receptors IL-1R, IL-1RA, IL-4RA were investigated. Angiotensin I-converting enzyme (ACE) gene polymorphism was carried out only in the group of patients to evaluate a possible association with known genetic risk factors for AD and cerebrovascular diseases. Our analysis showed an highly significant presence in AD patients when compared to controls of some alleles belonging to the anti-inflammatory cytokine gene IL-4 (C allele for the -590 promoter and T allele for the -1098, p <0.0006 and p <0.0005, respectively). Statistically no difference was evident for the D allele of the ACE gene in the group of demented patients. Although our observations suggest the presence of a pro-inflammatory environment in AD patients with MMSE <24, which is sustained by a low expression of anti-inflammatory cytokine genes, it is important to underline that these results could not apply to AD patients belonging to different ethnic groups, as the ethnic characteristics can influence the study of polymorphisms. Large cohort studies are necessary in order to assess the true association of some cytokine alleles or extended haplotypes with AD.