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Beta-Amyloid-Dependent miRNAs as Circulating Biomarkers in Alzheimer's Disease: a Preliminary Report
Seyedeh Nazanin Hajjri1,2, Saeed Sadigh-Eteghad2, Masoud Mehrpour3
1Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, Iran.
Abstract:
MicroRNAs (miRNAs) are considered among the most reliable biomarkers to diagnose and predict Alzheimer's disease (AD), due to their regulatory nature. The main goal of this study was to evaluate the expression of miR4422 and miR3714, as the main regulators of GSAP and BACE1 expression, in AD patients compared with healthy subjects. Twenty patients with a mild to moderate AD (58-71 years old) and 15 healthy subjects (58-73 years old) participated in this study. The expression levels of miR4422 and miR3714 as the target genes and 5S rRNA and miRlet7a-5p as the reference genes were measured in the two groups. To compare the expression between the case and the control groups, the t test or the Wilcoxon test was used, based on the data distribution patterns. The efficiencies of amplification of the miR4422, miR3714, 5S rRNA, and miRlet7a-5p genes all were in the acceptable range. The mean miR4422-5S rRNA dCt value was significantly different between the two groups (p = 0.018). The relative fold change of the expression was 0.43. The mean miR4422-miRlet7a-5p dCt value (p = 0.41), the mean miR3714-5S rRNA dCt value (p = 0.10), and the mean miR3714-miRlet7a-5p dCt value (p = 0.063) were not significantly different between the two groups. We indicated that miR4422 could be a reliable biomarker for Alzheimer's diagnosis. It seems that the reduced expression of miR4422 that targets GSAP and BACE1 expression can lead to an increase in the formation of Aβ plaque.
Insights
MicroRNA 4422 (miR4422) shows reduced expression in Alzheimer's disease (AD) patients, suggesting it's a reliable biomarker for AD diagnosis. Lower miR4422 may increase amyloid-beta plaque formation.
Area of Science:
- Biochemistry
- Molecular Biology
- Neuroscience
Background:
- MicroRNAs (miRNAs) are crucial gene regulators and potential biomarkers for neurodegenerative diseases.
- Alzheimer's disease (AD) is characterized by the accumulation of amyloid-beta (Aβ) plaques.
- GSAP and BACE1 are key enzymes involved in Aβ production, and their expression is regulated by miRNAs.
Purpose of the Study:
- To investigate the expression levels of miR4422 and miR3714 in Alzheimer's disease patients compared to healthy controls.
- To assess the potential of miR4422 and miR3714 as diagnostic biomarkers for Alzheimer's disease.
- To explore the relationship between these miRNAs and the expression of GSAP and BACE1 in AD.
Main Methods:
- Quantitative real-time PCR (qRT-PCR) was used to measure the expression of miR4422 and miR3714.
- Expression levels were normalized using reference genes (5S rRNA and miRlet7a-5p).
- Statistical analysis (t-test or Wilcoxon test) was performed to compare miRNA expression between AD patients and healthy subjects.
Main Results:
- A significant downregulation of miR4422 was observed in Alzheimer's disease patients compared to healthy controls (p=0.018).
- The relative fold change in miR4422 expression was 0.43.
- No significant differences in miR3714 expression were found between the groups when normalized to either 5S rRNA or miRlet7a-5p.
Conclusions:
- miR4422 is a potential and reliable biomarker for the diagnosis of Alzheimer's disease.
- Reduced expression of miR4422 may contribute to increased Aβ plaque formation by upregulating GSAP and BACE1.
- Further research is warranted to fully elucidate the role of miR4422 in Alzheimer's pathogenesis.
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