MicroRNAs (miRNAs) in the blood could provide a new way to diagnose mild cognitive impairment and predict the progression to dementia years before it is officially diagnosed, two studies suggest.
The findings could lead to greater understanding of the molecular mechanisms underlying the plaques, tangles and brain atrophy that are hallmarks of Alzheimer’s disease, and help lead to a screening in a point-of-care setting.
They could also provide clues to the next generation of therapeutic targets and present a less invasive and more cost-effective alternative to measuring β-amyloid (A) and tau (T) proteins and neurodegeneration (N) assessed in brain tissue, through brain imaging and investigations of cerebrospinal fluid and plasma.
“Our discovery is important because, unlike the current A/T/N biomarkers, microRNAs may serve as blood molecular biomarkers years before Alzheimer’s disease manifests clinically, thus identifying the time window for effective prevention or early intervention to stop the progression of Alzheimer’s,” said senior author Ivana Delalle, MD, PhD, a professor of pathology and laboratory medicine at Boston University.
The findings appear in two papers published in Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association.
MiRNAs are short non-coding RNAs that help maintain a healthy balance of proteins in the cell. They are very stable and control entire molecular pathways, making them useful as biomarkers.
Just a few miRNAs can provide information on complex changes involving pathways involving neuroinflammation, metabolic changes and synapse dysfunction.
In the first study, Delalle and co-workers compared baseline plasma miRNAs and A/T/N biomarkers from 803 participants in the the Alzheimer’s Disease Neuroimaging Initiative.
The team identified nine, two, and eight dysregulated miRNAs significantly associated with respective A/T/N biomarker positivity.
The team also identified Alzheimer’s disease biomarker-specific and common pathways related to miRNAs. MiRNAs improved the classification for A/T/N positivity by up to 9%.
In the second study, Kwangsik Nho, PhD, from Indiana School of Medicine, and colleagues examined the value of small RNA sequencing in plasma samples from 847 participants in the same initiative.
Through this, the team identified microRNA signatures that correlated with a diagnosis of Alzheimer’s disease, the most common form of dementia in the elderly.
They also found several miRNAs that could be used as biomarkers that could predict the development of Alzheimer’s disease after mild cognitive impairment.
Adding plasma microRNA levels to neuropsychological testing increased the accuracy by which Alzheimer’s disease could be predicted in patients with mild cognitive impairment.
“We have laid the groundwork for further investigations into the role of microRNAs in Alzheimer’s disease pathogenesis,” said Nho.
“We envision that once specific miRNA signatures are further confirmed, the analysis of blood miRNAs will be transferred to simple assay formats enabling the adoption of blood miRNAome analysis in clinical practice.”
