title: TNFR-associated factor-2 (TRAF-2) in Alzheimer's disease.
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.
authors: Dementia 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
authors: Doris
authors: D
authors: Culpan
authors: Dougal
authors: D
authors: Cram
authors: Kate
authors: K
authors: Chalmers
authors: Abigail
authors: A
authors: Cornish
authors: Laura
authors: L
authors: Palmer
authors: Jennifer
authors: J
authors: Palmer
authors: Anthony
authors: A
authors: Hughes
authors: Peter
authors: P
authors: Passmore
authors: David
authors: D
authors: Craig
authors: David
authors: D
authors: Craigs
authors: Gordon K
authors: GK
authors: Wilcock
authors: Patrick G
authors: PG
authors: Kehoe
authors: Seth
authors: S
authors: Love
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D001921:Brain / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D016022:Case-Control Studies; D015331:Cohort Studies; D004252:DNA Mutational Analysis; D005260:Female; D005625:Frontal Lobe / Q000378:metabolism / Q000473:pathology; D005787:Gene Frequency / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005820:Genetic Testing; D005838:Genotype; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D016874:Neurofibrillary Tangles / Q000378:metabolism / Q000473:pathology; D058225:Plaque, Amyloid / Q000378:metabolism / Q000473:pathology; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D012189:Retrospective Studies; D047992:TNF Receptor-Associated Factor 2 / Q000032:analysis / Q000235:genetics* / Q000378:metabolism
chemical_list: D012333:RNA, Messenger; D047992:TNF Receptor-Associated Factor 2