Are Circulating MicroRNAs Peripheral Biomarkers for Alzheimer’s Disease?

Subodh Kumar1 and P. Hemachandra Reddy1,2,3,4,5,6
1Garrison Institute on Aging, Texas Tech University Health Sciences Center, 3601 4th Street, MS
9424, Lubbock, Texas 79430
2Cell Biology & Biochemistry, Texas Tech University Health Sciences Center, 3601 4th Street, MS
9424, Lubbock, Texas 79430
3Neuroscience & Pharmacology, Texas Tech University Health Sciences Center, 3601 4th Street,
MS 9424, Lubbock, Texas 79430
4Neurology, Texas Tech University Health Sciences Center, 3601 4th Street, MS 9424, Lubbock,
Texas 79430
5Speech, Language and Hearing Sciences Departments, Texas Tech University Health Sciences
Center, 3601 4th Street, MS 9424, Lubbock, Texas 79430
6Garrison Institute on Aging, South West Campus, Texas Tech University Health Sciences Center,
6630 S. Quaker Ste. E, MS 7495, Lubbock, Texas 79413

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.

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