Alzheimer’s disease (AD) is a neurodegenerative disorder that preferenzially affects individuals above 60 years (yrs) with increasing risk in older ages. Neuropathological hallmarks of AD include brain atrophy, senile plaques and neurofibrillary tangles. There is also evidence that inflammatory processes may contribute to the development of AD through production of cytokines and free radicals that can damage and kill neurones.In this study, we have selected 25 late-onset AD patients (mean age 68 yrs) and 66 control subjects(CS) (mean age 64 yrs) without signs of dementia. AD diagnosis was performed according to DSM III R and NINDCS/ADRDA criteria. The Cytokine Genotyping Tray was used to analyze polymorphisms of the following cytokine genes: IL-1A,IL-1B,IL-1R,IL-1RA,IL-2,IL-4,IL-4RA,IL-6,IL-10,IL-2,TGFB,IFN-G,TNF-A. Genotype frequencies between AD patients and CS were compared using chi-square analysis and Fisher’s exact twotailed tests.The results showed an increased frequency in AD patients as compared to CS of: 1) the high-producer-174G/C gene promoter phenotype (p<0.019); 2) the homozygous haplotype -1082A/-819T/-592A which is associated with low IL-10 production (p<0.021); 3) IL-1A (-889)allele T homozigousity (p<0.03) as well as homozygousity of IL-1B (-511)allele T (p<0.005). The combined analysis of the latter two genotypes was found to confer a greater risk of AD (OR 7.7, p< 0.001).No correlation was found with the other cytokine gene polymorphisms. In conclusion, our data support the hypothesis that a pro-inflammatory phenotype is associated with late-onset AD likely contributing to the development and/or the progression of the disease.

The role of cytokine gene polymorphisms in Alzheimer's disease.

SANTORI, GREGORIO;
2004-01-01

Abstract

Alzheimer’s disease (AD) is a neurodegenerative disorder that preferenzially affects individuals above 60 years (yrs) with increasing risk in older ages. Neuropathological hallmarks of AD include brain atrophy, senile plaques and neurofibrillary tangles. There is also evidence that inflammatory processes may contribute to the development of AD through production of cytokines and free radicals that can damage and kill neurones.In this study, we have selected 25 late-onset AD patients (mean age 68 yrs) and 66 control subjects(CS) (mean age 64 yrs) without signs of dementia. AD diagnosis was performed according to DSM III R and NINDCS/ADRDA criteria. The Cytokine Genotyping Tray was used to analyze polymorphisms of the following cytokine genes: IL-1A,IL-1B,IL-1R,IL-1RA,IL-2,IL-4,IL-4RA,IL-6,IL-10,IL-2,TGFB,IFN-G,TNF-A. Genotype frequencies between AD patients and CS were compared using chi-square analysis and Fisher’s exact twotailed tests.The results showed an increased frequency in AD patients as compared to CS of: 1) the high-producer-174G/C gene promoter phenotype (p<0.019); 2) the homozygous haplotype -1082A/-819T/-592A which is associated with low IL-10 production (p<0.021); 3) IL-1A (-889)allele T homozigousity (p<0.03) as well as homozygousity of IL-1B (-511)allele T (p<0.005). The combined analysis of the latter two genotypes was found to confer a greater risk of AD (OR 7.7, p< 0.001).No correlation was found with the other cytokine gene polymorphisms. In conclusion, our data support the hypothesis that a pro-inflammatory phenotype is associated with late-onset AD likely contributing to the development and/or the progression of the disease.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11567/260432
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