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Plasma microRNA vary in association with the progression of Alzheimer's disease
Diane Guévremont1,2,3, Helen Tsui2,3,4, Robert Knight2,3,4
1Department of Anatomy University of Otago Dunedin New Zealand.
Introduction:
Early intervention in Alzheimer's disease (AD) requires the development of an easily administered test that is able to identify those at risk. Focusing on microRNA robustly detected in plasma and standardizing the analysis strategy, we sought to identify disease-stage specific biomarkers.
Methods:
Using TaqMan microfluidics arrays and a statistical consensus approach, we assessed plasma levels of 185 neurodegeneration-related microRNA, in cohorts of cognitively normal amyloid β-positive (CN-Aβ+), mild cognitive impairment (MCI), and Alzheimer's disease (AD) participants, relative to their respective controls.
Results:
Distinct disease stage microRNA biomarkers were identified, shown to predict membership of the groups (area under the curve [AUC] >0.8) and were altered dynamically with AD progression in a longitudinal study. Bioinformatics demonstrated that these microRNA target known AD-related pathways, such as the Phosphoinositide 3-kinase (PI3K-Akt) signalling pathway. Furthermore, a significant correlation was found between miR-27a-3p, miR-27b-3p, and miR-324-5p and amyloid beta load.
Discussion:
Our results show that microRNA signatures alter throughout the progression of AD, reflect the underlying disease pathology, and may prove to be useful diagnostic markers.
Insights
Early detection of Alzheimer's disease (AD) is possible using specific microRNA signatures found in plasma. These biomarkers reflect disease progression and underlying pathology, aiding in early diagnosis.
Area of Science:
- Biomarker discovery
- Neurodegenerative disease research
- Molecular diagnostics
Background:
- Early intervention for Alzheimer's disease (AD) necessitates accessible diagnostic tools.
- Plasma microRNAs are promising biomarkers due to their stability and detectability.
- Standardized analysis is crucial for reliable biomarker identification.
Purpose of the Study:
- To identify disease-stage specific microRNA biomarkers in Alzheimer's disease.
- To validate microRNA signatures as predictors of AD progression.
- To explore the correlation between microRNAs and amyloid beta load.
Main Methods:
- Assessed plasma levels of 185 neurodegeneration-related microRNAs using TaqMan microfluidics arrays.
- Employed a statistical consensus approach across cohorts: cognitively normal amyloid β-positive (CN-Aβ+), mild cognitive impairment (MCI), and Alzheimer's disease (AD).
- Conducted longitudinal analysis and bioinformatics to identify disease-stage specific microRNA signatures and their targeted pathways.
Main Results:
- Identified distinct microRNA signatures that predict group membership with high accuracy (AUC > 0.8).
- Observed dynamic alterations in microRNA levels correlating with AD progression in a longitudinal study.
- Found significant correlations between specific microRNAs (miR-27a-3p, miR-27b-3p, miR-324-5p) and amyloid beta load, and identified targeting of PI3K-Akt signaling pathway.
Conclusions:
- MicroRNA signatures change throughout Alzheimer's disease progression.
- These signatures reflect the underlying neuropathology of AD.
- Plasma microRNA profiles show potential as valuable diagnostic markers for Alzheimer's disease.
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