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Walter J. Lukiw, Y. Zhao, S. Bhattacharjee, J.G. Cui, N.G. Bazan; Elevated Expression Of a Pro-inflammatory, NF-kB-regulated micro RNA-146a (miRNA-146a) In The Primary Visual Cortex Of Late-stage Alzheimer's Disease (AD). Invest. Ophthalmol. Vis. Sci. 2011;52(14):3400.
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A significant up-regulation of pro-inflammatory signaling and pathogenic gene expression is observed in the hippocampus and association neocortex of Alzheimer's disease (AD) affected brain. While the primary visual cortex (Brodmann Area 17) is thought to be initially spared of AD-type change, in late stages of AD inflammatory neuropathology progressively spreads caudally into this primary sensory region. This is accompanied by visual disturbances that include impaired visual perception and hallucinations in advanced AD patients. The purpose of this study was to examine changes in micro RNA (miRNA) and messenger RNA (mRNA) complexity in the primary visual cortex during AD progression in moderate-stage to late-stage AD and age-matched controls. We focused on pro-inflammatory miRNAs such as the inducible, NF-kB-regulated miRNA-146a, and miRNA-146a mRNA targets known to be specifically affected in the AD neocortex and hippocampus.
Bioinformatics; DNA array; human brain post-mortem tissue; gel shift and supershift assay; micro-RNA array; Northern micro-dot blot analysis; RT-PCR; Western immunohistochemistry
The data indicate that in late-stage AD, a human association neocortex-enriched, pro-inflammatory, NF-kB-regulated miRNA-146a is significantly over-expressed, and a miRNA-146a target and repressor of complement signaling, complement factor H (CFH), is significantly under-expressed, as pro-inflammatory gene expression and neuropathology advance into the primary visual sensory areas.
These data provide the first example of an up-regulated miRNA-146a whose expression is significantly linked to advancing neuroinflammation, altered visual signal processing and visual disturbances associated with end-stages of the AD process.
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