title: Association of early-onset Alzheimer's disease with an interleukin-1alpha gene polymorphism.
abstract: 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.
authors.affiliation: Department of Neuroscience, University of Milano, Italy.
authors.forename: L M
authors.initials: LM
authors.lastname: Grimaldi
authors.forename: V M
authors.initials: VM
authors.lastname: Casadei
authors.forename: C
authors.initials: C
authors.lastname: Ferri
authors.forename: F
authors.initials: F
authors.lastname: Veglia
authors.forename: F
authors.initials: F
authors.lastname: Licastro
authors.forename: G
authors.initials: G
authors.lastname: Annoni
authors.forename: I
authors.initials: I
authors.lastname: Biunno
authors.forename: G
authors.initials: G
authors.lastname: De Bellis
authors.forename: S
authors.initials: S
authors.lastname: Sorbi
authors.forename: C
authors.initials: C
authors.lastname: Mariani
authors.forename: N
authors.initials: N
authors.lastname: Canal
authors.forename: W S
authors.initials: WS
authors.lastname: Griffin
authors.forename: M
authors.initials: M
authors.lastname: Franceschi
mesh_terms: 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
chemical_list: D007375:Interleukin-1