New biomarker for asymptomatic stages of Alzheimer’s disease
2024
University of Barcelona, Barcelona, Spain
Clinical relevance of miRNAs as biomarkers is growing due to their stability and detection in biofluids. Presently, diagnosis at asymptomatic stages of Alzheimer's disease (AD) remains a challenge since it can only be made at autopsy according to Braak NFT staging. Achieving the objective of detecting AD at early stages would allow possible therapies to be addressed before the onset of cognitive impairment. Many studies have determined that the expression pattern of some miRNAs is dysregulated in AD patients, but to date, none has been correlated with downregulated expression of cellular prion protein (PrPC) during disease progression. That is why, cross studies of miRNAs up-regulated in AD with in silico identification of potential miRNAs-binding to 3′UTR of human PRNP gene were conducted. In this study, miR-519a-3p was selected for analyses. In vitro experiments were carried out to validate miR-519a-3p target on 3′UTR-PRN, and to analyze the levels of PrPC expression after using of mimic technology in cell culture. In order to analyse miR-519a-3p expression in human cerebral samples of AD at different stages of disease evolution, RT-qPCR was performed. Additionally, samples of other neurodegenerative diseases such as other non-AD tauopathies and several synucleinopathies were included in the study. The results showed that miR-519a-3p overlaps with PRNP 3′UTR in vitro and promotes downregulation of PrPC. Moreover, miR-519a-3p was found to be up-regulated exclusively in AD samples from stage I to VI, suggesting its potential use as a novel label of preclinical stages of the disease.
miR-519a-3p, found to regulate cellular prion protein during Alzheimer's disease pathogenesis, as a biomarker of asymptomatic stages
Rosalina Gavín
Added on: 06-24-2024
[1] https://www.sciencedirect.com/science/article/pii/S0925443924001765
