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

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-a (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.