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The microRNA-1908 up-regulation in the peripheral blood cells impairs amyloid clearance by targeting ApoE

Z Wang1,2,3,4,5,6, W Qin1,2,3,4,5,6, C B Wei1,2,3,4,5,6

  • 1Inovation Center for Neurological Disorders, Department of Neurology, Xuan Wu Hospital, Capital Medical University, Beijing, China.

International Journal of Geriatric Psychiatry
|April 11, 2018
PubMed
Abstract

Insights

Alzheimer's disease (AD) patients show reduced ApoE levels and increased microRNA-1908. This microRNA-1908 inhibits ApoE, impacting amyloid-beta clearance, suggesting it as a potential therapeutic target for AD.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Genetics

Background:

  • Alzheimer's disease (AD) is a neurodegenerative disorder characterized by progressive cognitive decline.
  • Apolipoprotein E (ApoE) plays a crucial role in lipid transport and is implicated in AD pathogenesis.
  • MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression and are increasingly recognized for their role in diseases.

Purpose of the Study:

  • To investigate the relationship between ApoE dysregulation and microRNA-1908 in Alzheimer's disease.
  • To elucidate the mechanism by which microRNA-1908 affects ApoE expression and function.
  • To explore the potential of microRNA-1908 as a therapeutic target for AD.

Main Methods:

  • Plasma ApoE levels were quantified in AD patients and healthy controls using enzyme-linked immunosorbent assay (ELISA).
  • Quantitative real-time polymerase chain reaction (qRT-PCR) was used to measure microRNA and ApoE mRNA levels in cell lines.
  • In vitro experiments using THP-1 and U87 cell lines were conducted to assess the effect of microRNA-1908 on ApoE expression and Aβ clearance.

Main Results:

  • AD patients exhibited significantly lower plasma ApoE levels compared to controls.
  • MicroRNA-1908 was found to be upregulated in AD patients and negatively correlated with plasma ApoE levels.
  • MicroRNA-1908 directly targets the 3'untranslated region of ApoE mRNA, inhibiting both mRNA and protein expression and impairing ApoE-mediated Aβ clearance.

Conclusions:

  • MicroRNA-1908 plays a significant role in ApoE dysregulation observed in Alzheimer's disease.
  • The inhibitory effect of microRNA-1908 on ApoE suggests a novel mechanism contributing to AD pathogenesis.
  • MicroRNA-1908 represents a potential therapeutic target for the treatment of Alzheimer's disease.
Keywords:
ADApoEamyloidmicroRNA

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