Are circulating microRNAs peripheral biomarkers for Alzheimer's disease?

Subodh Kumar, P (Hemachandra) Reddy

Research output: Contribution to journalReview article

77 Citations (Scopus)

Abstract

Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by memory loss, multiple cognitive abnormalities and intellectual impairments. Currently, there are no drugs or agents that can delay and/or prevent the progression of disease in elderly individuals, and there are no peripheral biomarkers that can detect AD early in its pathogenesis. Research has focused on identifying biomarkers for AD so that treatment can be begun as soon as possible in order to restrict or prevent intellectual impairments, memory loss, and other cognitive abnormalities that are associated with the disease. One such potential biomarker is microRNAs that are found in circulatory biofluids, such as blood and blood components, serum and plasma. Blood and blood components are primary sources where miRNAs are released in either cell-free form and then bind to protein components, or are in an encapsulated form with microvesicle particles. Exosomal miRNAs are known to be stable in biofluids and can be detected by high throughput techniques, like microarray and RNA sequencing. In AD brain, enriched miRNAs encapsulated with exosomes crosses the blood brain barrier and secreted in the CSF and blood circulations. This review summarizes recent studies that have identified miRNAs in the blood, serum, plasma, exosomes, cerebral spinal fluids, and extracellular fluids as potential biomarkers of AD. Recent research has revealed only six miRNAs - miR-9, miR-125b, miR-146a, miR-181c, let-7g-5p, and miR-191-5p - that were reported by multiple investigators. Some studies analyzed the diagnostic potential of these six miRNAs through receiver operating curve analysis which indicates the significant area-under-curve values in different biofluid samples. miR-191-5p was found to have the maximum area-under-curve value (0.95) only in plasma and serum samples while smaller area-under-curve values were found for miR-125, miR-181c, miR-191-5p, miR-146a, and miR-9. This article shortlisted the promising miRNA candidates and discussed their diagnostic properties and cellular functions in order to search for potential biomarker for AD.

Original languageEnglish (US)
Pages (from-to)1617-1627
Number of pages11
JournalBiochimica et Biophysica Acta - Molecular Basis of Disease
Volume1862
Issue number9
DOIs
StatePublished - Sep 1 2016
Externally publishedYes

Fingerprint

MicroRNAs
Alzheimer Disease
Biomarkers
Exosomes
Area Under Curve
Memory Disorders
Serum
Multiple Abnormalities
RNA Sequence Analysis
Blood Circulation
Extracellular Fluid
Blood-Brain Barrier
Research
Neurodegenerative Diseases
Disease Progression
Research Personnel
Brain
Pharmaceutical Preparations
Proteins

Keywords

  • Alzheimer's disease
  • Biomarker
  • Cerebral spinal fluid
  • Circulatory microRNA
  • CSF
  • Plasma
  • Serum

ASJC Scopus subject areas

  • Molecular Biology
  • Molecular Medicine

Cite this

Are circulating microRNAs peripheral biomarkers for Alzheimer's disease? / Kumar, Subodh; Reddy, P (Hemachandra).

In: Biochimica et Biophysica Acta - Molecular Basis of Disease, Vol. 1862, No. 9, 01.09.2016, p. 1617-1627.

Research output: Contribution to journalReview article

Kumar, Subodh ; Reddy, P (Hemachandra). / Are circulating microRNAs peripheral biomarkers for Alzheimer's disease?. In: Biochimica et Biophysica Acta - Molecular Basis of Disease. 2016 ; Vol. 1862, No. 9. pp. 1617-1627.
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AB - Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by memory loss, multiple cognitive abnormalities and intellectual impairments. Currently, there are no drugs or agents that can delay and/or prevent the progression of disease in elderly individuals, and there are no peripheral biomarkers that can detect AD early in its pathogenesis. Research has focused on identifying biomarkers for AD so that treatment can be begun as soon as possible in order to restrict or prevent intellectual impairments, memory loss, and other cognitive abnormalities that are associated with the disease. One such potential biomarker is microRNAs that are found in circulatory biofluids, such as blood and blood components, serum and plasma. Blood and blood components are primary sources where miRNAs are released in either cell-free form and then bind to protein components, or are in an encapsulated form with microvesicle particles. Exosomal miRNAs are known to be stable in biofluids and can be detected by high throughput techniques, like microarray and RNA sequencing. In AD brain, enriched miRNAs encapsulated with exosomes crosses the blood brain barrier and secreted in the CSF and blood circulations. This review summarizes recent studies that have identified miRNAs in the blood, serum, plasma, exosomes, cerebral spinal fluids, and extracellular fluids as potential biomarkers of AD. Recent research has revealed only six miRNAs - miR-9, miR-125b, miR-146a, miR-181c, let-7g-5p, and miR-191-5p - that were reported by multiple investigators. Some studies analyzed the diagnostic potential of these six miRNAs through receiver operating curve analysis which indicates the significant area-under-curve values in different biofluid samples. miR-191-5p was found to have the maximum area-under-curve value (0.95) only in plasma and serum samples while smaller area-under-curve values were found for miR-125, miR-181c, miR-191-5p, miR-146a, and miR-9. This article shortlisted the promising miRNA candidates and discussed their diagnostic properties and cellular functions in order to search for potential biomarker for AD.

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