Protein and gene expression of tumour necrosis factor receptors I and II and their promoter gene polymorphisms in Alzheimer's disease.
The levels of pro-inflammatory cytokines, such as tumour necrosis factor-alpha (TNF-alpha), are increased in the brain in Alzheimer's disease (AD). Most of the biological properties of TNF-alpha are mediated through its two receptors, tumour necrosis factor receptors I and II (TNF-RI and TNF-RII). We have used immunohistochemistry, Western blotting and real time-PCR (RT-PCR) on frontal (BA 6/24) and temporal (BA 20-22) neocortex and hippocampus from AD and control brains to determine if both receptor proteins were present and expressed in AD and if sequence variations (SNPs) in the promoter regions of the two genes are associated with AD. Expression of TNF-RI exceeded that of TNF-RII in AD and control brains at protein and mRNA levels. The level of TNF-RI protein varied considerably in individual brains but not between AD and control brains. None of the identified TNF-RI and -RII SNPs in the promoter regions of the genes was linked with AD. Our findings suggest that TNF-RI and -RII promoter gene polymorphisms and variations in protein and gene expression of these receptors are unlikely to play a major role in the development of AD.
Culpan
Doris
D
Dementia Research Group, Institute of Clinical Neurosciences, Department of Clinical Sciences at North Bristol, University of Bristol, Frenchay Hospital, Frenchay, Bristol, United Kingdom. Doris.Culpan@bristol.ac.uk
Cornish
Abigail
A
Love
Seth
S
Kehoe
Patrick G
PG
Wilcock
Gordon K
GK
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics* / Q000378:metabolism*; D001483:Base Sequence; D001921:Brain / Q000378:metabolism; D016022:Case-Control Studies; D005260:Female; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000235:genetics* / Q000378:metabolism*; D047889:Receptors, Tumor Necrosis Factor, Type II / Q000235:genetics* / Q000378:metabolism*; D012189:Retrospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction
D012333:RNA, Messenger; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II