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The role of Aβ circRNA in Alzheimer’s disease

Dingding Mo
doi: https://doi.org/10.1101/260968
Dingding Mo
Max Planck Institute for Biology of Ageing, Joseph-Stelzmann-Strasse 9b, 50931 Cologne, Germany
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  • For correspondence: Dingding.Mo@age.mpg.de
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Abstract

Circular RNAs are universally expressed and evolutionarily conserved; however, the functions of most circRNAs are still unknown. Previous studies have shown that circRNAs are enriched in neurons and accumulate during brain ageing, indicating possible roles in ageing-associated neurodegenerative disorders. Alzheimer’s disease (AD) is the most common detrimental dementia, closely linked with advancing age. Amyloid-β (Aβ) peptide accumulation due to APP proteolytic processing is long believed to be the key step in AD neuropathology. Mutations in factors involved in Aβ peptide biogenesis have been shown to contribute to the mechanism of familial AD (FAD). However, this accounts for less than 1-5% of total AD patients, and mechanisms for the most common type of sporadic AD (SAD), remain largely unknown. Here, I demonstrate that a circRNA is expressed from the wild-type APP gene in human brain, encompassing the Aβ peptide sequence. Using my previously established circRNA expression strategy, I found Aβ circRNA-encoded expression of an Aβ related peptide, called Aβ circRNA-derived peptide, which up-regulates GSK3β levels and tau phosphorylation, both hallmarks of AD progression. Thus, Aβ circRNA and its translated peptide may not only play a causative role in AD, but represent promising therapeutic targets in AD diagnosis and treatment.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted February 06, 2018.
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The role of Aβ circRNA in Alzheimer’s disease
Dingding Mo
bioRxiv 260968; doi: https://doi.org/10.1101/260968
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The role of Aβ circRNA in Alzheimer’s disease
Dingding Mo
bioRxiv 260968; doi: https://doi.org/10.1101/260968

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