circRNA from APP Gene Changes in Alzheimer's Disease Human Brain

Alzheimer's disease (AD) is the most common cause of age-related dementia. Amyloid precursor protein (APP) is the precursor of A beta peptides, and its role in AD has been widely investigated. Recently, it has been reported that a circular RNA (circRNA) originated from APP gene can serve as a template for A beta synthesis, postulating it as an alternative pathway for the A beta biogenesis. Moreover, circRNAs play important roles in brain development and in neurological diseases. Therefore, our aim was to study the expression of a circAPP (hsa_circ_0007556) and its linear cognate in AD human entorhinal cortex, a brain region most vulnerable to AD pathology. First, we confirmed the presence of circAPP (hsa_circ_0007556) in human entorhinal cortex samples using RT-PCR and Sanger sequencing of PCR products. Next, a 0.49-fold decrease in circAPP (hsa_circ_0007556) levels was observed in entorhinal cortex of AD cases compared to controls (p-value < 0.05) by qPCR. In contrast, APP mRNA expression did not show changes in the entorhinal cortex between AD cases and controls (Fold-change = 1.06; p-value = 0.81). A negative correlation was found between A beta deposits and circAPP (hsa_circ_0007556) and APP expression levels (Rho Spearman = -0.56, p-value < 0.001 and Rho Spearman = -0.44, p-values < 0.001, respectively). Finally, by using bioinformatics tools, 17 miRNAs were predicted to bind circAPP (hsa_circ_0007556), and the functional analysis predicted that they were involved in some pathways, such as the Wnt-signaling pathway (p = 3.32 x 10(-6)). Long-term potentiation (p = 2.86 x 10(-5)), among others, is known to be altered in AD. To sum up, we show that circAPP (hsa_circ_0007556) is deregulated in the entorhinal cortex of AD patients. These results add to the notion that circAPP (hsa_circ_0007556) could be playing a role in the pathogenesis of AD disease.