A Hayes

Publications (4)13.23 Total impact

• Source

  Available from: nih.gov

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

  A Hayes, E K Green, A Pritchard, J M Harris, Y Zhang, J C Lambert, M C Chartier-Harlin, S M Pickering-Brown, C L Lendon, D M A Mann
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  ABSTRACT: 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. 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. 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. 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.
  Journal of Neurology Neurosurgery &amp Psychiatry 11/2004; 75(10):1475-7. · 4.76 Impact Factor
• Source

  Available from: nih.gov

  Article: Association of 3'-UTR polymorphisms of the oxidised LDL receptor 1 (OLR1) gene with Alzheimer's disease.

  J-C Lambert, E Luedecking-Zimmer, S Merrot, A Hayes, U Thaker, P Desai, A Houzet, X Hermant, D Cottel, A Pritchard, T Iwatsubo, F Pasquier, B Frigard, P M Conneally, M-C Chartier-Harlin, S T DeKosky, C Lendon, D Mann, M I Kamboh, P Amouyel
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  ABSTRACT: Although possession of the epsilon 4 allele of the apolipoprotein E gene appears to be an important biological marker for Alzheimer's disease (AD) susceptibility, strong evidence indicates that at least one additional risk gene exists on chromosome 12. Here, we describe an association of the 3'-UTR +1073 C/T polymorphism of the OLR1 (oxidised LDL receptor 1) on chromosome 12 with AD in French sporadic (589 cases and 663 controls) and American familial (230 affected sibs and 143 unaffected sibs) populations. The age and sex adjusted odds ratio between the CC+CT genotypes versus the TT genotypes was 1.56 (p=0.001) in the French sample and 1.92 (p=0.02) in the American sample. Furthermore, we have discovered a new T/A polymorphism two bases upstream of the +1073 C/T polymorphism. This +1071 T/A polymorphism was not associated with the disease, although it may weakly modulate the impact of the +1073 C/T polymorphism. Using 3'-UTR sequence probes, we have observed specific DNA protein binding with nuclear proteins from lymphocyte, astrocytoma, and neuroblastoma cell lines, but not from the microglia cell line. This binding was modified by both the +1071 T/A and +1073 C/T polymorphisms. In addition, a trend was observed between the presence or absence of the +1073 C allele and the level of astrocytic activation in the brain of AD cases. However, Abeta(40), Abeta(42), Abeta total, and Tau loads or the level of microglial cell activation were not modulated by the 3'-UTR OLR1 polymorphisms. Finally, we assessed the impact of these polymorphisms on the level of OLR1 expression in lymphocytes from AD cases compared with controls. The OLR1 expression was significantly lower in AD cases bearing the CC and CT genotypes compared with controls with the same genotypes. In conclusion, our data suggest that genetic variation in the OLR1 gene may modify the risk of AD.
  Journal of Medical Genetics 07/2003; 40(6):424-30. · 6.36 Impact Factor
• Article: Pathological relationships between microglial cell activity and tau and amyloid beta protein in patients with Alzheimer's disease.

  A Hayes, U Thaker, T Iwatsubo, S M Pickering-Brown, D M A Mann
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  ABSTRACT: The extent of microglial cell activation (microglial cell load) was estimated by image analysis of ferritin-immunostained sections of frontal cortex from 72 patients with pathologically confirmed Alzheimer's disease (AD), and correlated with the amount of pathological tau and amyloid beta protein (Abeta), as both Abeta(40) and Abeta(42) load, in adjacent sections of the same cases. Microglial cell load did not correlate with either Abeta(40) or Abeta(42) load but was significantly correlated with pathological tau load. Microglial cell load was unrelated to age at onset of disease or duration of illness. It is possible that because the presence of microglial cells predates that of pathological tau proteins within the cerebral cortex in AD, neurofibrillary damage to nerve cells may stem from the release of proinflammatory and other potentially neurotoxic molecules from microglial cells.
  Neuroscience Letters 11/2002; 331(3):171-4. · 2.11 Impact Factor
• Article: Association of 3'-UTR polymorphisms of the oxidised LDL receptor 1 (OLR1) gene with Alzheimer’s disease

  J C Lambert, E Luedecking-Zimmer, S Merrot, A Hayes, U Thaker, P Desai, A Houzet, X Hermant, D Cottel, A Pritchard, T Iwatsubo, F Pasquier, B Frigard, P M Conneally, M C Chartier-Harlin, S T DeKosky, C Lendon, D Mann, M I Kamboh, P Amouyel