The role of -850 tumor necrosis factor-alfa and apolipoprotein E genetic polymorphism in patients with Down?s syndrome-related dementia

Down’s syndrome (DS) is a disease with a complex etiology. Tumor necrosis factor-alfa (TNF-alfa) (6p21.3) and apolipoprotein E (APOE) (19q13.2) are candidate genes as they interact with the brain deposition of Abeta, one of the neuropathological hallmarks in DS. We examined 136 DS patients and 113 controls for -850 TNF-alfa and APOE polymorphisms. The -850T frequency in DS was significantly higher than in controls while the APOE E4 allele was negatively selected in patients compared to normal subjects. Our findings suggest that the -850T allele, which is more common among patients at high risk of dementia such as those with DS, might eventually play a role in the development of dementia; no inference on the role of the allele APOE E4 in DS-related dementia may be derived from our results.