Gender-Dependent Deregulation of Linear and Circular RNA Variants of HOMER1 in the Entorhinal Cortex of Alzheimer's Disease.

The gene is involved in synaptic plasticity, learning and memory. Recent studies show that circular RNA derived from () expression is altered in some Alzheimer's disease (AD) brain regions. In addition, messenger (mRNA) levels have been associated with β-Amyloid (Aβ) deposits in brain cortical regions. Our aim was to measure the expression levels of circRNAs and their linear forms in the human AD entorhinal cortex. First, we showed downregulation of and mRNA and hsa_circ_0006916 and hsa_circ_0073127 levels in AD female cases compared to controls by RT-qPCR. A positive correlation was observed between , mRNA, and hsa_circ_0073128 with HOMER1B/C protein only in females. Global average area of Aβ deposits in entorhinal cortex samples was negatively correlated with , mRNA, and hsa_circ_0073127 in both genders. Furthermore, no differences in DNA methylation were found in two regions of promoter between AD cases and controls. To sum up, we demonstrate that linear and circular RNA variants of are downregulated in the entorhinal cortex of female patients with AD. These results add to the notion that and its circular forms could be playing a female-specific role in the pathogenesis of AD.