Association of alleles carried at TNFA -850 and BAT1-22 with Alzheimers diseaseReportar como inadecuado

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Journal of Neuroinflammation

, 5:36

First Online: 20 August 2008Received: 26 June 2008Accepted: 20 August 2008


BackgroundInflammatory changes are a prominent feature of brains affected by Alzheimer-s disease AD. Activated glial cells release inflammatory cytokines which modulate the neurodegenerative process. These cytokines are encoded by genes representing several interleukins and TNFA, which are associated with AD. The gene coding for HLA-B associated transcript 1 BAT1 lies adjacent to TNFA in the central major histocompatibility complex MHC. BAT1, a member of the DEAD-box family of RNA helicases, appears to regulate the production of inflammatory cytokines associated with AD pathology. In the current study TNFA and BAT1 promoter polymorphisms were analysed in AD and control cases and BAT1 mRNA levels were investigated in brain tissue from AD and control cases.

MethodsGenotyping was performed for polymorphisms at positions -850 and -308 in the proximal promoter of TNFA and position -22 in the promoter of BAT1. These were investigated singly or in haplotypic association in a cohort of Australian AD patients with AD stratified on the basis of their APOE ε4 genotype. Semi-quantitative RT-PCR was also performed for BAT1 from RNA isolated from brain tissue from AD and control cases.

ResultsAPOE ε4 was associated with an independent increase in risk for AD in individuals with TNFA -850*2, while carriage of BAT1 -22*2 reduced the risk for AD, independent of APOE ε4 genotype. Semi-quantitative mRNA analysis in human brain tissue showed elevated levels of BAT1 mRNA in frontal cortex of AD cases.

ConclusionThese findings lend support to the application of TNFA and BAT1 polymorphisms in early diagnosis or risk assessment strategies for AD and suggest a potential role for BAT1 in the regulation of inflammatory reactions in AD pathology.

Electronic supplementary materialThe online version of this article doi:10.1186-1742-2094-5-36 contains supplementary material, which is available to authorized users.

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Autor: Anastazija Gnjec - Katarzyna J D-Costa - Simon M Laws - Ross Hedley - Kelvin Balakrishnan - Kevin Taddei - Georgia Martin


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