Lower expression level of two RAGE alternative splicing isoforms in Alzheimer's disease

Alternative splicing (AS) is a common phenomenon in gene expression of eukaryotic organisms, especially in mammals, producing multiple gene isoforms from a single gene that involve in physiological and pathological processes. Receptor for advanced glycation end products (RAGE) has multiple AS isoforms with significant tissue and organism specificity. RAGE signaling has been reported involved in the onset and development of Alzheimer's disease (AD) and the roles of RAGE AS isoforms have not yet been fully illustrated in AD pathogenesis. In the present study, two of RAGE AS isoforms (RAGEΔ and sRAGEΔ) were investigated in the human brain specimens from AD and age-matched control subjects. The expression of these isoforms was found brain-region specific, and significant lower expression levels of both RAGEΔ and sRAGEΔ were detected in multiple brain regions of AD subjects than control subjects. Data indicated tight association between the AS isoforms (RAGEΔ and sRAGEΔ) and neurodegeneration. An antagonistic pairing model has been suggested to explain the working mechanism of AS isoforms on gene regulation and pathological development.