Objective: To investigate the impact of possession of the -889 C/T polymorphi sm of the interleukin 1A gene (IL-1A) and the -511 C/T polymorphism of the int erleukin 1B gene (IL-1B) on the extent of neuroinflammation ...Objective: To investigate the impact of possession of the -889 C/T polymorphi sm of the interleukin 1A gene (IL-1A) and the -511 C/T polymorphism of the int erleukin 1B gene (IL-1B) on the extent of neuroinflammation in the brain in Alz heimers disease (AD), as demonstrated by the degree of microglial cell activit y associated with each IL-1A and IL-1B genotype. Method: Microglial cell activ ity within the frontal cortex was determined in 68 patients with necropsy confir med AD by image analysis as the percentage area of tissue occupied by ferritin i mmunostained material (microglial cell load). IL-1A, IL-1B, and apolipoprotein E (APOE) genotyping were performed by polymerase chain reaction on DNA extracte d from frontal cortex or cerebellum. Results: The microglial cell load was 31%g reater in patients with IL-1A T allele, 62%greater with IL1A TT genotype, but 108%greater with IL-1A TT genotype in combination with APOE 4 allele. No effec ts on microglial cell load occurred with polymorphisms in IL-1B, or APOE alone. Conclusions: Polymorphisms within IL-1A influence the degree of brain microgli al cell activation, especially in bearers of APOE 4 allele, reinforcing the impo rtance of neuroinflammatory processes in the pathogenesis of AD, and supporting the rationale for treating the disease with inflammation modulating drugs.展开更多
文摘Objective: To investigate the impact of possession of the -889 C/T polymorphi sm of the interleukin 1A gene (IL-1A) and the -511 C/T polymorphism of the int erleukin 1B gene (IL-1B) on the extent of neuroinflammation in the brain in Alz heimers disease (AD), as demonstrated by the degree of microglial cell activit y associated with each IL-1A and IL-1B genotype. Method: Microglial cell activ ity within the frontal cortex was determined in 68 patients with necropsy confir med AD by image analysis as the percentage area of tissue occupied by ferritin i mmunostained material (microglial cell load). IL-1A, IL-1B, and apolipoprotein E (APOE) genotyping were performed by polymerase chain reaction on DNA extracte d from frontal cortex or cerebellum. Results: The microglial cell load was 31%g reater in patients with IL-1A T allele, 62%greater with IL1A TT genotype, but 108%greater with IL-1A TT genotype in combination with APOE 4 allele. No effec ts on microglial cell load occurred with polymorphisms in IL-1B, or APOE alone. Conclusions: Polymorphisms within IL-1A influence the degree of brain microgli al cell activation, especially in bearers of APOE 4 allele, reinforcing the impo rtance of neuroinflammatory processes in the pathogenesis of AD, and supporting the rationale for treating the disease with inflammation modulating drugs.
