Predicting progression to dementia using blood-based microRNA: A chance for early intervention?
Alzheimer’s Disease (AD) is the most common cause of dementia worldwide, with approximately 46 million people affected and a predicted prevalence of over 130 million by 2050.
At present, there is no therapy available that targets the disease pathogenesis and a common belief is that instigating treatment after a diagnosis of AD is too late as the neuronal damage is irreversible. AD is a devastating illness for patients, their families and society as a whole, with many affected by the disease in some capacity.
In the study available here, Dr Tobias Engel and his team at RCSI University of Medicine and Health Sciences, in collaboration with Trinity College Dublin and clinicians from Spain, have explored methods of identifying patients with a diagnosis of mild cognitive impairment (MCI) who will suffer further cognitive decline and go on to develop dementia. Their research reveals a biomarker that can be potentially used to predict this progression and inform early intervention treatment.
Dr Engel’s team recognised the need for a cost-effective and practical biomarker for predicting the risk of progression from MCI to AD. It hence focused on microRNAs (miRNAs) derived from peripheral blood samples.
These molecules act as post-transcriptional regulators of protein expression in the cell. In the central nervous system, they are vital for neuronal homeostasis. They also have the unique benefits of being easily quantifiable and stable in extracellular environments.
The study was comprised of two cohorts. Firstly, a discovery cohort which included 31 control patients, 30 patients with MCI and 25 patients with AD was investigated, followed by a longitudinal cohort that included three groups, each containing six patients with distinct cognitive progressions. These groups included cognitively healthy patients who progressed to stable MCI, in addition to cognitively healthy patients and MCI patients who progressed to dementia.
Using the discovery cohort, the team were able to identify Let-7b and miRNA-206 as potential biomarkers for AD pathology with increased concentrations in the blood plasma of the MCI and AD subjects.
A detailed analysis of the MCI group from the discovery cohort showed that miR-206 plasma levels were significantly higher in MCI patients who went on to progress further towards dementia when compared to patients remaining at an MCI stage, demonstrating the prognostic potential of blood-based miRNAs.
Researchers then evaluated the selected miRNAs for relationships with cognitive decline and conversion from MCI to dementia based on annual clinical evaluations over 4–5 years.
In line with findings from the discovery cohort, miRNA-206 plasma levels were significantly higher in MCI patients with a high risk of dementia, as well as in MCI patients with deteriorating cognitive assessment scores over the four years. The stable MCI group showed little or no change in miRNA-206 levels over the 4–5 year follow up, while 83% of the cognitively healthy group who progressed to dementia had increased levels of miRNA-206 at the 4–5 year follow up.
The research led by Dr Engel’s team successfully demonstrates that miRNA-206 in the blood is a viable biomarker for AD and for predicting the conversion from MCI to dementia. Going forward, this may allow the development of a simple, minimally invasive and cost-effective test for AD development and prodromal dementia. This work might also allow for the earlier implementation of treatment that can slow or halt the pathogenesis of AD and hence prevent the progression from MCI to dementia before it is too late.
Journal Article Information:
Elevated Plasma microRNA-206 Levels Predict Cognitive Decline and Progression to Dementia from Mild Cognitive Impairment
Biomolecules 2019, 9(11), 734