Cytokine polymorphisms and Alzheimer disease: possible associations.

Alzheimer's disease (AD) is a degenerative dementia characterized by typical, destructive alterations of neurons (neurofibrillary tangles and amyloid plaques), and glial proliferation. Cytokine-driven inflammatory environment can contribute to the pathogenesis and/or progression of the disease. The aim of the study was to evaluate and compare genotypic and allelic polymorphisms of 13 cytokine genes in 19 Caucasoid AD patients with medium-high level of dementia (assessed by an MMSE < 24) and 20 normal controls affected by non inflammatory neuropsychiatric disease. Polymorphisms in the genes of IL-lA, IL-lB, IL-2, IL-4, IL-6, IL-10, IL-12, IFN-G, TGF-beta, TNF-alpha, and of the cytokine receptors IL-lR, IL-IRA, IL-4RA were investigated. APO-E and ACE gene polymorphisms were carried out in the patient's group only to evaluate a possible association with known genetic risk factors for AD. A highly significant presence of some alleles belonging to anti-inflammatory cytokine genes was found; particularly the C allele for the -590 promoter and T allele for the -1098 promoter of IL-4 appeared in a significantly higher percentage as compared with controls (P < 0.0006 and P < 0.0005, respectively), while a lesser significance was observed for the allele C of the -819 promoter of IL-10 (P < 0.03). Finally, in the group of demented patients for the APO-E gene we found a statistically significant presence of the E4 allele, whereas no difference was found for the polymorphisms of the ACE gene. Our observations corroborate the possible presence of a pro-inflammatory environment in AD patients, partly sustained by the low expression of anti-inflammatory cytokine genes when defined alleles are present. Large cohort studies are necessary in order to assess the real association of some cytokine alleles or haplotypes with AD.