The role of Aβ circRNA in Alzheimer's disease: alternative mechanism of Aβ biogenesis from Aβ circRNA translation

Abstract

Alzheimers disease (AD) is an age-related detrimental dementia. Amyloid beta peptides (A{beta}) play a crucial role in the pathology of AD. In familial AD, A{beta} is generated from the full-length amyloid precursor protein (APP) via dysregulated proteolytic processing. However, A{beta} biogenesis in case of sporadic AD remains so far elusive. circRNAs are a class of transcripts, which are preferentially expressed in brain. Here, we identified a circRNA (circA{beta}-a) derived from the A{beta}-coding region of the APP gene. circA{beta}-a is expressed in brains of AD and nondementia controls. With the aid of our recently established approach for analysis of circRNA functions, we demonstrated that circA{beta}-a is efficiently translated into a novel A{beta}-related A{beta}175 protein in living cells. Importantly, A{beta}175 was further processed to A{beta} peptides, the hallmark of AD. In summary, our analysis revealed alternative route of A{beta} biogenesis. circA{beta}-a and its corresponding protein might represent novel therapeutic targets for AD treatment.