Association of early-onset Alzheimer's disease with an interleukin-1alpha gene polymorphism.
Overexpression of the pluripotent cytokine interleukin-1 (IL-1) by microglial cells correlates with formation of neuritic beta-amyloid plaques in Alzheimer's disease (AD). We evaluated polymorphisms in the genes coding for the IL-1alpha, IL-1beta, and IL-1 receptor antagonist cytokines, and tested their association with the occurrence and age at onset of sporadic AD. We found a strong association between the IL-1A T/T genotype and AD onset before 65 years of age (odds ratio, 4.86), with carriers of this genotype showing an onset of disease 9 years earlier than IL-1A C/C carriers. A weaker association with the age at onset was also shown for the IL-1B and IL-1RN genes. These data suggest either a direct effect of the IL-1 gene family, mainly IL-1A, on the clinical onset of AD, or a linkage dysequilibrium with an unknown locus relevant to AD on chromosome 2.
Grimaldi
L M
LM
Department of Neuroscience, University of Milano, Italy.
Casadei
V M
VM
Ferri
C
C
Veglia
F
F
Licastro
F
F
Annoni
G
G
Biunno
I
I
De Bellis
G
G
Sorbi
S
S
Mariani
C
C
Canal
N
N
Griffin
W S
WS
Franceschi
M
M
D000328:Adult; D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000209:etiology / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D007375:Interleukin-1 / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics*; D012307:Risk Factors
D007375:Interleukin-1