Tumor necrosis factor-alpha -308 A/G polymorphism is associated with age at onset of Alzheimer’s disease

Giusi Irma Forte, Giuseppina Colonna Romano, Calogero Caruso, Giuseppina Candore, Letizia Scola, Domenico Lio, Carlo Vergani, Giuseppina Colonna-Romano, Giorgio Annoni, Letizia Scola, Antonino Crivello, Beatrice Arosio, Giusi Irma Forte, Domenico Lio, Giuseppina Candore, Federico Licastro, Calogero Caruso, Lorenza Galimberti, Antonino Crivello

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70 Citazioni (Scopus)


Pro-inflammatory cytokines and acute-phase proteins play an important role in Alzheimer's disease (AD) neurodegeneration, and common polymorphisms of genes controlling their production have been shown to be associated with AD. Tumor necrosis factor (TNF)-alpha is an inflammatory cytokine involved in the local immune response occurring in the central nervous system of AD patients. Genetic variation could contribute to the risk of developing AD or influence the age at the onset of the disease. We genotyped 222 patients (152 women, 70 men; age range 60-87) and 240 non-demented age-matched healthy controls for TNF-alpha -308 G/A single nucleotide polymorphism (SNP). No significant differences were observed in genotyped frequencies between patients and controls, whereas carriers of -308A showed a significantly lower mean age at onset than non-carriers of this allele. This difference was more evident taking into account ApolipoproteinE (ApoE) status since the lowest age at onset was observed in patients carrying the -308ATNF+/APOE4+ genotypes. In conclusion, our data support previous suggestions that, at least in Caucasians, the TNF gene is a disease modifier gene in patients in which AD is rising, bringing to light the importance of genetic variation at the pro-inflammatory components in the progression of AD.
Lingua originaleEnglish
pagine (da-a):567-571
RivistaMechanisms of Ageing and Development
Stato di pubblicazionePublished - 2006

All Science Journal Classification (ASJC) codes

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