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MicroRNA-455-3p as a Potential Biomarker for Alzheimer's Disease: An Update
Subodh Kumar1, P Hemachandra Reddy1,2,3,4,5,6,1
1Garrison Institute on Aging, Texas Tech University Health Sciences Center, Lubbock, TX, United States.
Abstract:
A non-invasive and early-detectable peripheral biomarker is urgently needed for Alzheimer's disease (AD). The present study is a step forward to verify the biomarker properties of human microRNA-455-3p (Hsa-miR-455-3p) in AD patients. Our previous findings on mild cognitive impaired subjects, AD patients and AD cells and mouse models unveiled the miR-455-3p as a potential peripheral biomarker for AD. In the current study, we verified the differential expression of miR-455-3p in postmortem AD brains obtained from NIH NeuroBioBank, and fibroblasts and B-lymphocytes from both familial and sporadic AD patients from Coriell Cell Repository of National Institutes on Aging. Total RNA was extracted from the fibroblasts, B-lymphocytes and AD postmortem brains, and expression of miR-455-3p was measured by real-time reverse-transcriptase RT-PCR. Our real-time RT-PCR analysis showed a significant (P = 0.0002) upregulation of miR-455-3p expression in AD postmortem brains compared to healthy control samples. Expression of miR-455-3p was also upregulated in the fibroblasts from AD patients, however a significant difference in miR-455-3p level was observed in the cells from sporadic AD patients (P = 0.014) compared to healthy controls. Similarly, in B-lymphocytes, miR-455-3p level was also higher (P = 0.044) especially in sporadic AD cases compared to controls. Receiver operating characteristic (ROC) curve analysis indicated the significant area under ROC curve (AUROC) value of miR-455-3p in AD postmortem brain (AUROC = 0.792; P = 0.001) and AD fibroblasts cells (AUROC = 0.861; P = 0.03), whereas in B-lymphocytes AUROC value of miR-455-3p was not significant. Further, in-silico analysis for miRNA targets predictions showed the binding capacity of miR-455-3p with several AD associated key genes such as APP, NGF, USP25, PDRG1, SMAD4, UBQLN1, SMAD2, TP73, VAMP2, HSPBAP1, and NRXN1. Hence, these observations further revealed that miR-455-3p is a potential biomarker for AD and its possible therapeutic target for AD.
Insights
Researchers identified human microRNA-455-3p (Hsa-miR-455-3p) as a promising Alzheimer's disease (AD) biomarker. This microRNA is upregulated in AD brains and patient cells, suggesting its potential for early AD detection and therapy.
Area of Science:
- Neuroscience
- Molecular Biology
- Biomarker Discovery
Background:
- Alzheimer's disease (AD) lacks non-invasive, early-detectable peripheral biomarkers.
- Previous studies indicated human microRNA-455-3p (Hsa-miR-455-3p) as a potential AD biomarker in preliminary models.
- Urgent need for reliable biomarkers for early diagnosis and therapeutic intervention in AD.
Purpose of the Study:
- To verify the biomarker properties of Hsa-miR-455-3p in Alzheimer's disease patients.
- To investigate the differential expression of Hsa-miR-455-3p in postmortem AD brains and patient-derived cells.
- To explore the potential of Hsa-miR-455-3p as a diagnostic biomarker and therapeutic target for AD.
Main Methods:
- Real-time reverse-transcriptase RT-PCR was used to measure Hsa-miR-455-3p expression.
- Analysis was performed on postmortem brain tissue, fibroblasts, and B-lymphocytes from AD patients and healthy controls.
- Receiver operating characteristic (ROC) curve analysis and in-silico target prediction were conducted.
Main Results:
- Significant upregulation of Hsa-miR-455-3p was observed in AD postmortem brains (P = 0.0002).
- Upregulation of Hsa-miR-455-3p was also found in AD fibroblasts (P = 0.014 for sporadic AD) and B-lymphocytes (P = 0.044 for sporadic AD).
- ROC analysis showed significant diagnostic potential for Hsa-miR-455-3p in AD postmortem brain and fibroblasts.
Conclusions:
- Hsa-miR-455-3p is a significantly upregulated molecule in Alzheimer's disease.
- Hsa-miR-455-3p demonstrates potential as a peripheral biomarker for AD diagnosis, particularly in fibroblasts.
- Hsa-miR-455-3p may serve as a therapeutic target for Alzheimer's disease, given its interaction with key AD-associated genes.