Association between the TNFalpha-308 A/G polymorphism and the onset-age of Alzheimer disease

Local inflammatory processes associated with amyloid plaques would contribute to the progression of late-onset Alzheimer disease (LOAD). Tumor necrosis factors alpha (TNF(alpha)) and beta (LT(alpha)) are inflammatory cytokines involved in the local immune response occurring in the central nervous system of LOAD patients. Genetic variation at these genes could contribute to the risk of developing AD or influence the age at the onset of the disease. We genotyped 315 LOAD patients and 400 healthy controls for DNA-polymorphisms in the genes encoding TNF(alpha) (-308 G/A, -238G/A) and LT(alpha) (Asn26Thr). Carriers of -308A showed a mean age at onset 3 years younger than noncarriers of this allele (P = 0.019). Our data suggest an effect of the TNF(alpha)-308 polymorphism on the age at onset of late AD. This represents additional evidence of the importance of genetic variation at the proinflammatory components in the origin and progression of this common neurodegenerative disease.