Alzheimer\u2019s 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 \u201cin vitro\u201d and \u201cin vivo\u201d 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\u2013SSP methodology), we have examined 22 polymorphisms in 13 cytokine genes in 63 caucasian AD patients with medium\u2013high 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-1\u3b2, IL-2, IL-4, IL-6, IL-10, IL-12, IFN-\u3b3, TGF-\u3b2, TNF-\u3b1 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
