Circulating miRNAs as biomarkers for diagnosis of mild cognitive impairment and Alzheimer's disease
Inventors
Miñano Molina, Alfredo Jesus • Siedlecki Wullich, Dolores • RODRIGUEZ ALVAREZ, JOSE
Assignees
Universitat Autonoma de Barcelona UAB • Centro de Investigacion Biomedica en Red de Enfermedades Neurodegenerativas CIBERNED
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Publication Number
US-12054779-B2
Publication Date
2024-08-06
Expiration Date
Abstract
The invention relates to a specific panel of circulating synaptic protein related miRNAs for use in the diagnosis of Mild Cognitive Impairment (MCI) and/or early diagnosis of Alzheimer's disease (AD). The invention also relates to a method and to a kit for the diagnosis of said diseases using said specific panel of circulating miRNAs biomarkers.
Core Innovation
The invention provides an in vitro method of diagnosis of Mild Cognitive Impairment (MCI) and/or early stages of Alzheimer's disease (AD) in an isolated biological sample of a subject. The method quantifies the expression level of a panel of miRNAs comprising miR-92a-3p, miR-181c-5p and miR-210-3p in the isolated biological sample.
The quantified miRNA value obtained from the subject is compared to a standard value. When the value obtained for the panel in the sample is significantly higher than the standard value, the subject is assigned to the group of patients suffering from MCI and/or early stages of AD.
The method uses an isolated biological sample selected from blood, serum, or plasma, and quantifying the expression level includes contacting the sample with miRNA-specific primers or probes for detection and/or quantification. The approach is supported by data showing upregulation of the three miRNAs in MCI/AD compared to healthy controls and reports a lack of change in frontotemporal dementia (FTD).
Claims Coverage
The independently claimed inventive concept is an in vitro diagnostic method for MCI and/or early-stage AD based on quantifying a three-miRNA panel and assigning the subject when the measured panel value is significantly higher than a standard value. The coverage includes one independent claim with dependent refinements that fix the sample context, detection modality, and miRNA identity.
In vitro diagnostic method for MCI and/or early stages of AD using a three-miRNA panel
An in vitro method of diagnosis of Mild Cognitive Impairment (MCI) and/or early stages of Alzheimer's disease (AD) in an isolated biological sample comprising quantifying the expression level of a panel of miRNAs comprising miR-92a-3p, miR-181c-5p and miR-210-3p, comparing the obtained value to a standard value, and assigning the subject to the group of patients suffering from MCI and/or early stages of AD when the obtained value is significantly higher than the standard value.
Use of an isolated biological sample matrix
The method uses an isolated biological sample selected from blood, serum, or plasma.
Quantifying miRNA expression using specified nucleic-acid assay modalities
Step (a) quantifying the expression level is performed using PCR, quantitative PCR (qPCR), RT-qPCR, droplet digital PCR, or Southern blot.
Fixed miRNA panel composition with SEQ ID numbers
The panel of miRNAs consists of miR-92a-3p, miR-181c-5p, and miR-210-3p with the listed SEQ ID numbers.
Primer/probe contacting for miRNA panel quantification
Quantifying the expression level of a panel of miRNAs includes contacting the sample with miRNA-specific primers or probes for detection and/or quantification.
Across the independent claim and its refinements, the claim scope centers on measuring the expression of a defined three-miRNA panel, comparing the measured panel value to a standard, and assigning MCI/early-stage AD status when the measured value is significantly higher. Dependent claims further restrict the biological sample matrix, the nucleic-acid assay modality, and the primer/probe contacting aspect of quantification.
Stated Advantages
Allows diagnostic assignment of subjects to the group of patients suffering from MCI and/or early stages of AD when the quantified miRNA panel value is significantly higher than a standard value.
Shows upregulation of the three miRNAs in MCI/AD versus healthy controls and provides ROC/AUC performance for individual and combined markers.
Reports lack of change in frontotemporal dementia (FTD).
Follow-up indicates higher miRNA signature levels in MCI patients who later progress to AD.
Documented Applications
Diagnosing Mild Cognitive Impairment (MCI) and/or early stages of Alzheimer's disease (AD) using a plasma miRNA biomarker panel in an isolated biological sample, including assigning subjects based on comparison to a standard value.
Differentiating MCI/AD from frontotemporal dementia (FTD), based on reported lack of change in FTD.
Prognostic follow-up of MCI patients, where higher miRNA signature levels are reported in those who later progress to AD.
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