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Plasma microRNAs as potential biomarkers in early Alzheimer disease expression
Carmen Peña-Bautista1, Adrián Tarazona-Sánchez1, Aitana Braza-Boils2
1Alzheimer Disease Research Group, Instituto de Investigación Sanitaria La Fe, Avda de Fernando Abril Martorell, 106, 46026, Valencia, Spain.
Abstract:
The microRNAs (miRNAs) are potential biomarkers for complex pathologies due to their involvement in the regulation of several pathways. Alzheimer Disease (AD) requires new biomarkers in minimally invasive samples that allow an early diagnosis. The aim of this work is to study miRNAS as potential AD biomarkers and their role in the pathology development. In this study, participants (n = 46) were classified into mild cognitive impairment due to AD (MCI-AD, n = 19), preclinical AD (n = 8) and healthy elderly controls (n = 19), according to CSF biomarkers levels (amyloid β42, total tau, phosphorylated tau) and neuropsychological assessment. Then, plasma miRNAomic expression profiles were analysed by Next Generation Sequencing. Finally, the selected miRNAs were validated by quantitative PCR (q-PCR). A panel of 11 miRNAs was selected from omics expression analysis, and 8 of them were validated by q-PCR. Individually, they did not show statistically significant differences among participant groups. However, a multivariate model including these 8 miRNAs revealed a potential association with AD for three of them. Specifically, relatively lower expression levels of miR-92a-3p and miR-486-5p are observed in AD patients, and relatively higher levels of miR-29a-3p are observed in AD patients. These biomarkers could be involved in the regulation of pathways such as synaptic transmission, structural functions, cell signalling and metabolism or transcription regulation. Some plasma miRNAs (miRNA-92a-3p, miRNA-486-5p, miRNA-29a-3p) are slightly dysregulated in AD, being potential biomarkers of the pathology. However, more studies with a large sample size should be carried out to verify these results, as well as to further investigate the mechanisms of action of these miRNAs.
Insights
This study identifies three plasma microRNAs (miRNAs) as potential biomarkers for Alzheimer Disease (AD). Lower levels of miR-92a-3p and miR-486-5p, and higher levels of miR-29a-3p, show potential association with AD pathology.
Area of Science:
- Neuroscience
- Biomarker Discovery
- Molecular Biology
Background:
- Alzheimer Disease (AD) requires novel biomarkers for early diagnosis using minimally invasive samples.
- MicroRNAs (miRNAs) are regulators of biological pathways and potential biomarkers for complex diseases like AD.
Purpose of the Study:
- To investigate plasma miRNAs as potential biomarkers for Alzheimer Disease (AD).
- To explore the role of specific miRNAs in AD pathology development.
Main Methods:
- Plasma miRNA expression profiling using Next Generation Sequencing in participants with mild cognitive impairment due to AD (MCI-AD), preclinical AD, and healthy controls.
- Validation of selected miRNAs using quantitative PCR (q-PCR).
- Classification of participants based on cerebrospinal fluid (CSF) biomarkers and neuropsychological assessment.
Main Results:
- A panel of 11 miRNAs was initially selected, with 8 validated by q-PCR.
- Individually, the validated miRNAs did not show significant differences between groups.
- A multivariate model indicated potential AD association for three miRNAs: lower miR-92a-3p and miR-486-5p, and higher miR-29a-3p levels in AD patients.
Conclusions:
- Plasma miR-92a-3p, miR-486-5p, and miR-29a-3p show slight dysregulation in AD and may serve as potential biomarkers.
- These miRNAs could be involved in regulating pathways crucial to AD pathogenesis.
- Further large-scale studies are needed to validate these findings and elucidate their mechanisms.
