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Plasma microRNA biomarkers for detection of mild cognitive impairment
Kira S Sheinerman1, Vladimir G Tsivinsky, Fiona Crawford
1DiamiR, LLC, Princeton, NJ 08540, USA.
Abstract:
Early stages of many neurodegenerative diseases, such as Alzheimer's disease, vascular and frontotemporal dementia, and Parkinson's disease, are frequently associated with Mild Cognitive Impairment (MCI). A minimally invasive screening test for early detection of MCI may be used to select optimal patient groups in clinical trials, to monitor disease progression and response to treatment, and to better plan patient clinical care. Here, we examined the feasibility of using pairs of brain-enriched plasma microRNA (miRNA), at least one of which is enriched in synapses and neurites, as biomarkers that could differentiate patients with MCI from age-matched controls. The identified biomarker pairs fall into two sets: the "miR-132 family" (miR-128/miR-491-5p, miR-132/miR-491-5p and mir-874/miR-491-5p) and the "miR-134 family" (miR-134/miR-370, miR-323-3p/miR-370 and miR-382/miR-370). The area under the Receiver-Operating Characteristic curve for the differentiation of MCI from controls using these biomarker pairs is 0.91-0.95, with sensitivity and specificity at 79%-100% (miR-132 family) and 79%-95% (miR-134 family), and p〈0.001. In a separate longitudinal study, the identified miRNA biomarker pairs successfully detected MCI in majority of patients at asymptomatic stage 1-5 years prior to clinical diagnosis. The reported biomarker pairs also appear useful for detecting age-related brain changes. Further testing in a larger study is necessary for validation of these results.
Insights
Pairs of brain-enriched plasma microRNAs show promise for early detection of Mild Cognitive Impairment (MCI). These biomarkers can identify MCI patients years before clinical diagnosis, aiding clinical trials and patient care.
Area of Science:
- Neuroscience
- Biomarker Discovery
- Genetics
Background:
- Mild Cognitive Impairment (MCI) is an early indicator of neurodegenerative diseases like Alzheimer's.
- Early detection of MCI is crucial for clinical trials, treatment monitoring, and patient management.
- Current diagnostic methods may not be sufficiently sensitive for early-stage detection.
Purpose of the Study:
- To investigate the feasibility of using plasma microRNA (miRNA) pairs as biomarkers for differentiating MCI from controls.
- To identify specific miRNA pairs enriched in synapses and neurites for enhanced diagnostic accuracy.
- To assess the potential of these biomarkers for detecting MCI at asymptomatic stages and age-related cognitive changes.
Main Methods:
- Analysis of brain-enriched plasma microRNAs, focusing on those linked to synaptic and neuritic functions.
- Utilized Receiver Operating Characteristic (ROC) curve analysis to evaluate biomarker pair performance.
- Conducted a longitudinal study to assess the predictive capability of identified miRNA biomarkers.
Main Results:
- Identified two sets of miRNA biomarker pairs: the "miR-132 family" and the "miR-134 family".
- Achieved high diagnostic accuracy with Area Under the Curve (AUC) values of 0.91-0.95 for differentiating MCI.
- Demonstrated successful detection of MCI in a majority of patients 1-5 years prior to clinical diagnosis, including at asymptomatic stages.
Conclusions:
- Specific plasma miRNA pairs show significant potential as minimally invasive biomarkers for early MCI detection.
- The identified "miR-132" and "miR-134" families can differentiate MCI patients from controls with high sensitivity and specificity.
- These biomarkers may aid in early intervention, patient stratification for clinical trials, and monitoring age-related cognitive decline, warranting further validation.
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