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.
Ribizzi
G
G
Department of Neurology, Ospedale S. Martino, L.go R. Benzi, 10, 16100, Genoa, Italy. gribizz1@tin.it
Fiordoro
S
S
Barocci
S
S
Ferrari
E
E
Megna
M
M
D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D000544:Alzheimer Disease / Q000235:genetics*; D001057:Apolipoproteins E / Q000235:genetics; D016022:Case-Control Studies; D016207:Cytokines / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D007378:Interleukins / Q000235:genetics; D008297:Male; D001523:Mental Disorders / Q000235:genetics; D008875:Middle Aged; D009483:Neuropsychological Tests; D007703:Peptidyl-Dipeptidase A / Q000235:genetics; D011110:Polymorphism, Genetic; D012307:Risk Factors; D012720:Severity of Illness Index; D044465:White People / Q000235:genetics
D001057:Apolipoproteins E; D016207:Cytokines; D007378:Interleukins; C488034:ACE protein, human; D007703:Peptidyl-Dipeptidase A