TNFR-associated factor-2 (TRAF-2) in Alzheimer's disease.
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.
Culpan
Doris
D
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
Cram
Dougal
D
Chalmers
Kate
K
Cornish
Abigail
A
Palmer
Laura
L
Palmer
Jennifer
J
Hughes
Anthony
A
Passmore
Peter
P
Craig
David
D
Craigs
David
D
Wilcock
Gordon K
GK
Kehoe
Patrick G
PG
Love
Seth
S
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
D012333:RNA, Messenger; D047992:TNF Receptor-Associated Factor 2