TY - JOUR
T1 - A polymorphic variation in the interleukin 1A gene increases brain microglial cell activity in Alzheimer's disease
AU - Hayes, A.
AU - Green, E. K.
AU - Pritchard, A.
AU - Harris, J. M.
AU - Zhang, Y.
AU - Lambert, J. C.
AU - Chartier-Harlin, M. C.
AU - Pickering-Brown, S. M.
AU - Lendon, C. L.
AU - Mann, D. M A
PY - 2004/10
Y1 - 2004/10
N2 - Objective: To investigate the impact of possession of the -889 C/T polymorphism of the interleukin 1A gene (IL-1A) and the -511 C/T polymorphism of the interleukin 1B gene (IL-1B) on the extent of neuroinflammation in the brain in Alzheimer's disease (AD), as demonstrated by the degree of microglial cell activity associated with each IL-1A and IL-1B genotype. 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 ε4 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 ε4 allele, reinforcing the importance of neuroinflammatory processes in the pathogenesis of AD, and supporting the rationale for treating the disease with inflammation modulating drugs.
AB - Objective: To investigate the impact of possession of the -889 C/T polymorphism of the interleukin 1A gene (IL-1A) and the -511 C/T polymorphism of the interleukin 1B gene (IL-1B) on the extent of neuroinflammation in the brain in Alzheimer's disease (AD), as demonstrated by the degree of microglial cell activity associated with each IL-1A and IL-1B genotype. 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 ε4 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 ε4 allele, reinforcing the importance of neuroinflammatory processes in the pathogenesis of AD, and supporting the rationale for treating the disease with inflammation modulating drugs.
U2 - 10.1136/jnnp.2003.030866
DO - 10.1136/jnnp.2003.030866
M3 - Article
SN - 0022-3050
VL - 75
SP - 1475
EP - 1477
JO - Journal of Neurology, Neurosurgery and Psychiatry
JF - Journal of Neurology, Neurosurgery and Psychiatry
IS - 10
ER -