A polymorphic variation in the interleukin 1A gene increases brain microglial cell activity in Alzheimer's disease

Method: Microglial cell activity within the frontal cortex was determined in 68 patients with necropsy confirmed AD by image analysis as the percentage area of tissue occupied by ferritin immunostained material (microglial cell load). IL-1A, IL-1B, and apolipoprotein E (APOE) genotyping were performed by polymerase chain reaction on DNA extracted from frontal cortex or cerebellum. Results: The microglial cell load was 31% greater in patients with IL-1A T allele, 62% greater with IL-1A TT genotype, but 108% greater with IL-1A TT genotype in combination with APOE e4 allele. No effects on microglial cell load occurred with polymorphisms in IL-1B, or APOE alone. Conclusions: Polymorphisms within IL-1A influence the degree of brain microglial cell activation, especially in bearers of APOE e4 allele, reinforcing the importance of neuroinflammatory processes in the pathogenesis of AD, and supporting the rationale for treating the disease with inflammation modulating drugs.