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


METHODS
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 epsilon4 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 epsilon4 allele, reinforcing the importance of neuroinflammatory processes in the pathogenesis of AD, and supporting the rationale for treating the disease with inflammation modulating drugs.
Hayes
A
A
Neuroscience Research Group, University of Manchester, Greater Manchester Neurosciences Centre, Hope Hospital, Salford M6 8HD, UK.
Green
E K
EK
Pritchard
A
A
Harris
J M
JM
Zhang
Y
Y
Lambert
J C
JC
Chartier-Harlin
M C
MC
Pickering-Brown
S M
SM
Lendon
C L
CL
Mann
D M A
DM
D000328:Adult; D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics* / Q000503:physiopathology*; D001057:Apolipoproteins E / Q000235:genetics; D001344:Autopsy; D002455:Cell Division; D005260:Female; D005838:Genotype; D006801:Humans; D007375:Interleukin-1 / Q000235:genetics*; D008297:Male; D017628:Microglia / Q000166:cytology* / Q000502:physiology*; D008875:Middle Aged; D011110:Polymorphism, Genetic
D001057:Apolipoproteins E; D007375:Interleukin-1