RNA Transcription in Alzheimer's Disease Brain and Its Implication in Mitochondrial Dysfunction.

Genes (Basel)

Geriatric Research, Education, and Clinical Center, VA Puget Sound Health Care System, Seattle, WA 98108, USA.

Published: June 2021

Increasing evidence suggests that the Translocase of Outer Mitochondria Membrane 40 () gene may contribute to the risk of Alzheimer's disease (AD). Currently, there is no consensus as to whether expression is up- or down-regulated in AD brains, hindering a clear interpretation of 's role in this disease. The aim of this study was to determine if RNA levels differ between AD and control brains. We applied RT-qPCR to study transcription in human postmortem brain (PMB) and assessed associations of these RNA levels with genetic variants in and We also compared RNA levels with mitochondrial functions in human cell lines. Initially, we found that the human genome carries multiple pseudogenes capable of producing highly homologous RNAs that can obscure precise RNA measurements. To circumvent this obstacle, we developed a novel RNA expression assay targeting the primary transcript of . Using this assay, we showed that RNA was upregulated in AD PMB. Additionally, elevated RNA levels were associated with decreases in mitochondrial DNA copy number and mitochondrial membrane potential in oxidative stress-challenged cells. Overall, differential transcription of RNA in the brain is associated with AD and could be an indicator of mitochondrial dysfunction.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8226536PMC
http://dx.doi.org/10.3390/genes12060871DOI Listing

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