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TNFR-associated factor-2 (TRAF-2) in Alzheimer's disease
Doris Culpan1, Dougal Cram, Kate Chalmers
1Dementia Research Group, Institute of Clinical Neurosciences, Department of Clinical Sciences at North Bristol, University of Bristol, John James Buildings, Frenchay Hospital, Bristol, United Kingdom. Doris.Culpan@bristol.ac.uk
Abstract:
Levels of tumor necrosis factor-alpha (TNF-alpha) are increased in the brain in Alzheimer's disease (AD). The TNF-alpha/TNF-R signaling pathways involve complex interactions between several proteins, including TNF-receptor-associated factor-2 (TRAF-2). We have examined the distribution and levels of TRAF-2 in AD and control brains and also whether single nucleotide polymorphisms (SNPs) in the TRAF-2 gene are associated with AD and influence TRAF-2 expression. Immunohistochemistry demonstrated TRAF-2 in AD and control cortex in neurons, within plaque-associated neurites and some neurofibrillary tangles. Western blots revealed a band of the expected apparent molecular mass (approximately 50kDa) for TRAF-2, in homogenates of AD and control cortex. RT-PCR showed the levels of TRAF-2 mRNA to be significantly higher in the frontal cortex of AD than control brains (p=0.015). TRAF-2 mRNA expression was not linked to any SNPs. The 3' UTR SNP (rs7852970) GG allele was significantly protective against AD (p=0.030). Our findings suggest that the TRAF-2 pathway is involved AD. The mechanisms are currently unclear and need further examination.
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