@article{a3ddcf03e6c34393ba8b7eb7a82687ee,
title = "Association of alleles carried at TNFA -850 and BAT1 -22 with Alzheimer's disease",
abstract = "Background: Inflammatory 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. Methods: Genotyping 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. Results: APOE 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. Conclusion: These 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.",
author = "Anastazija Gnjec and D'Costa, {Katarzyna J.} and Laws, {Simon M.} and Ross Hedley and Kelvin Balakrishnan and Kevin Taddei and Georgia Martins and Athena Paton and Giuseppe Verdile and Gandy, {Samuel E.} and Anthony, {G. Anthony} and Brooks, {William S.} and Hayley Bennett and Olivier Piguet and Patricia Price and Judith Miklossy and Joachim Hallmayer and McGeer, {Patrick L.} and Martins, {Ralph N.}",
note = "Funding Information: Total RNA and protein was isolated from brain tissue (frontal cortex) samples from subjects with histopathologically confirmed definite AD and control cases without any AD pathology. Autopsy was performed within 48 hours after death. Subjects with PS1 mutations and a number of familial AD cases with APOE ε4 genotypes were from local pedigrees and from the brain tissue bank of Drexel University College of Medicine (Philadelphia, PA, USA). Control brain tissue was obtained locally (Western Australia) and tissues were also received from the New South Wales (NSW) Tissue Resource Centre (Sydney, NSW, Australia), which is supported by The University of Sydney, Neuroscience Institute of Schizophrenia and Allied Disorders, National Institute of Alcohol Abuse and Alcoholism and NSW Department of Health. Funding Information: This project was supported by the McCusker Foundation for Alzheimer's Disease Research, Edith Cowan University and Hollywood Private Hospital, Department of Veteran Affairs and the NHMRC. The authors would also like to acknowledge the excellent help in form of statistical analysis contributed by Dr Karen Josebury. Furthermore, the authors would like to acknowledge the Sir Zelman Cowen Universities' Fund which provided funding for collection of blood samples. We thank Dr Noel Tan for dissection and histopathological examination of brains. We also extend our thanks to Dr Clive Cooke (Queen Elizabeth Medical Centre, Perth, WA, Australia) for dissection and macroscopic examination of brains. Furthermore, we would like to thank Professor Glenda Halliday (Prince of Wales Medical Research Institute, Randwick, NSW, Australia) for valuable discussion with regard to the brain samples used.",
year = "2008",
month = aug,
day = "20",
doi = "10.1186/1742-2094-5-36",
language = "English",
volume = "5",
journal = "Journal of Neuroinflammation",
issn = "1742-2094",
publisher = "BioMed Central Ltd.",
}