Written by Charlotte Harrison, Science Writer
Alzheimer’s disease (AD) slowly destroys cognitive functioning — thinking, remembering and reasoning — and behavioural abilities so that eventually, patients cannot carry out even simple tasks. One of the key goals of AD research is to identify biomarkers that can predict disease before symptoms become apparent.
The potential of microRNAs (miR) as candidate biomarkers for predicting and diagnosing neuro‐degenerative diseases such as AD is an active area of research. Indeed, several miRNAs are known to be overexpressed at different stages of AD. A new paper published in Experimental And Therapeutic Medicine shows that two specific microRNAs — miR‐4722‐5p and miR‐615‐3p — are together a possible biomarker for AD that could be detected using a simple blood test.
The study analysed the relative mRNA expression levels of miR‐4722‐5p and miR‐615‐3p in blood samples from 33 patients with AD and 33 healthy controls. The level of the two mRNAs was higher in patients with AD than in controls. This finding was mirrored in a cell-based model of AD, β‐amyloid(25‐35)‐induced PC12 cells.
The authors then tested the diagnostic potential of the two mRNAs. A higher expression of miR‐4722‐5p and miR‐615‐3p in the blood samples was associated with a more severe cognitive decline, as determined by the patient’s score in a clinical test of dementia. The combination of the two miRNAs had a better diagnostic value than each miRNA alone.
Target genes and pathways
MicroRNAs can regulate gene expression and hence cellular signalling, so the authors investigated the target genes and pathways of the two miRNAs. The target genes of miR‐4722‐5p are likely involved in the catabolism of the signalling molecule cAMP, which has been linked to synaptic plasticity and memory deficits. In addition, miR‐4722‐5p target genes are likely linked to mTOR, a protein kinase that regulates autophagy and plays an important role in neurodegenerative diseases.
The target genes of miR‐615‐3p likely regulate pathways involving the FoxO transcription factor, which is involved in apoptosis and autophagy, as well as ErbB receptor tyrosine kinases.
Overall, this study adds to the growing body of evidence indicating that miRNAs are promising non‐invasive biomarkers that could enable the early detection of AD and ultimately lead to better treatments that target the underlying pathogenesis of AD.
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