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Int J Mol Epidemiol Genet 2011;2(2):156-162

Original Article
Tumour necrosis factor-α (TNF-α) and miRNA expression in frontal and
temporal neocortex in Alzheimer’s disease and the effect of TNF-α on miRNA
expression in vitro

Doris Culpan, Patrick G Kehoe and Seth Love

Dementia Research Group, School of Clinical Sciences, University of Bristol, John James Buildings, Frenchay Hospital,
Frenchay, Bristol, BS16 1LE, United Kingdom

Received January 11, 2011; accepted March 21, 2011; Epub March 25, 2011; published May 15, 2011

Abstract: Micro-RNAs (miRNAs) are short non-coding RNAs capable of regulating gene expression at the translational level. A
number of studies have suggested that the expression of several miRNAs is changed in AD. The pro-inflammatory cytokine
tumour necrosis factor-α (TNF-α) is increased in serum and CSF in AD. We measured the expression of TNFA and several AD
candidate gene-associated miRNAs (let7a/b, miR-128a/b, miR-27a/b, miR-155) in frontal and temporal neocortex from AD and
control brains. The expression of these miRNAs was also measured after incubating non-differentiated (NDC) and retinoic acid
-differentiated (DC) SH-SY5Y neuroblastoma cells with TNF-α. TNFA expression was similar in AD and control brains but miR-
128a/b levels were significantly reduced in the temporal cortex and miR-128b in the frontal cortex in AD. MiRNA levels did not
correlate with TNFA expression in brain tissue but exposure of NDC and DC SH-SY5Y cells to TNF-α caused a variable dose-
dependent response in the level of some of the miRNAs studied. Our brain tissue findings argue against a role for TNF-α in
influencing the expression of these miRNAs in AD. (IJMEG1101001).

Keywords: Alzheimer’s disease, tumour necrosis factor-α, microRNA, SH-SY5Y cells

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Address all correspondence to:
Doris Culpan
Dementia Research Group, School of Clinical Sciences
University of Bristol, John James Building, Frenchay Hospital
Frenchay, Bristol, BS16 1LE, United Kingdom
Tel:    0117 3403068
Fax:   0117 957 3955
E-mail:
Doris.Culpan@bristol.ac.uk