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Analysis of RNA from Alzheimer’s Disease Post-mortem Brain Tissues

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Abstract

Alzheimer’s disease (AD) is a uniquely human, age-related central nervous system (CNS) disorder for which there is no adequate experimental model. While well over 100 transgenic murine models of AD (TgAD) have been developed that recapitulate many of the neuropathological features of AD, key pathological features of AD such as progressive neuronal atrophy, neuron cell loss, and neurofibrillary tangle (NFT) formation have not been observed in any TgAD model to date. To more completely analyze and understand the neuropathology, altered neuro-inflammatory and innate-immune signaling pathways, and the complex molecular-genetics and epigenetics of AD, it is therefore necessary to rigorously examine short post-mortem interval (PMI) human brain tissues to gain a deeper and more thorough insight into the neuropathological mechanisms that characterize the AD process. This perspective-methods paper will highlight some important recent findings on the utilization of short PMI tissues in sporadic (idiopathic; of unknown origin) AD research with focus on the extraction and quantification of RNA, and in particular microRNA (miRNA) and messenger RNA (mRNA) and analytical strategies, drawing on the authors’ combined 125 years of laboratory experience into this investigative research area. We sincerely hope that new investigators in the field of “gene expression analysis in neurological disease” will benefit from the observations presented here and incorporate these recent findings and observations into their future experimental planning and design.

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Abbreviations

AD:

Alzheimer’s disease

ALU:

Alu human genomic repeated sequence (~300 base pair)

CNS:

Central nervous system

EEG:

Electroencephalogram

mRNA:

Messenger RNA

miRNA:

Micro RNA

PMI:

Post-mortem interval

TgAD:

Transgenic animal model of AD

TREM2:

Triggering receptor expressed in myeloid/microglial cells

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Acknowledgments

This research was presented in part at the Society for Neuroscience 44th Annual Meeting, Washington DC, USA, 14–19 November 2014. Thanks are extended to Drs. Yuhai Zhao, Surjyadipta Bhattacharjee, Aileen Pogue, and Darlene Guillot for the helpful discussions and expert technical assistance. Research on neurotoxic metals, small non-coding RNA, microRNA, the innate-immune response, amyloidogenesis, neuroinflammation, possible viral contribution to the AD process in the Clement, Culicchia, Dua, Hill, and Lukiw laboratories using extensive neuropathological and molecular genetic analysis of post-mortem brain tissues and bioinformatics analysis was supported through the Alzheimer Association, an unrestricted grant from Research to Prevent Blindness (RPB), the Louisiana Biotechnology Research Network (LBRN), and NIH grants NEI EY006311 and NIA AG038834.

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Authors and Affiliations

  1. Infectious Diseases, Experimental Therapeutics and Human Toxicology Lab, Southern University at New Orleans, New Orleans, LA, 70126, USA

    Christian Clement

  2. LSU Department of Ophthalmology, Louisiana State University Health Science Center, New Orleans, LA, 70112, USA

    James M. Hill & Walter J. Lukiw

  3. LSU Neuroscience Center of Excellence, Louisiana State University Health Sciences Center, New Orleans, LA, 70112, USA

    James M. Hill & Walter J. Lukiw

  4. Department of Health Information Management, Louisiana State University, Ruston, LA, 71270, USA

    Prerna Dua

  5. Department of Neurosurgery, Louisiana State University Health Science Center, New Orleans, LA, 70112, USA

    Frank Culicchia

  6. Department of Neurology, Louisiana State University Health Science Center, New Orleans, LA, 70112, USA

    Walter J. Lukiw

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  1. Christian Clement
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  2. James M. Hill
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  5. Walter J. Lukiw
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Corresponding author

Correspondence to Walter J. Lukiw.

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Clement, C., Hill, J.M., Dua, P. et al. Analysis of RNA from Alzheimer’s Disease Post-mortem Brain Tissues. Mol Neurobiol 53, 1322–1328 (2016). https://doi.org/10.1007/s12035-015-9105-6

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  • DOI: https://doi.org/10.1007/s12035-015-9105-6

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