Circulating microRNAs as Biomarkers of Alzheimer's Disease: A Systematic Review.
BACKGROUND
In recent years, microRNAs (miRNA), a class of non-coding RNA known to regulate protein expression post-transcriptionally, have been recognized as novel biomarkers of diseases.


OBJECTIVE
In this systematic review, we identify miRNAs that are differentially expressed in Alzheimer's disease (AD) and/or mild cognitive impairment (MCI) and evaluate their accuracy as potential blood biomarkers.


METHODS
Eligible studies of miRNAs in peripheral blood distinguishing patients with AD or MCI from cognitively normal controls were identified through standardized search strategies in Medline, PubMed, and Embase. MiRNAs that were differentially expressed were identified and where available their sensitivity and specificity for AD or MCI extracted from the retrieved studies.


RESULTS
Eighteen studies investigated the diagnostic value of miRNAs as peripheral biomarkers of AD/MCI. Twenty miRNAs were significantly upregulated and 32 miRNAs downregulated in AD compared to controls in ten AD studies. Nine miRNAs were consistently dysregulated in more than one study. Of the 8 MCI studies, only one miRNA, miR-132, was consistently upregulated in three independent studies. Of the studies that reported diagnostic accuracy data, the majority of miRNA panels and individual miRNAs had a sensitivity and specificity greater than 0.75.


CONCLUSIONS
Individual studies suggest that miRNAs can differentiate patients with AD/MCI from cognitively normal controls with modest accuracy. However, the literature is constrained by methodological differences between studies, with few studies assessing the same miRNAs. To become potential biomarkers for AD, further studies with standardized study designs for replication and validation are required. Results from this review may help researchers select candidate miRNAs for further investigation.
Centre for Healthy Brain and Ageing, School of Psychiatry, UNSW, Sydney, Australia.|Primary Dementia Collaborative Research Centre, UNSW, Sydney, Australia.
Helen Zong Ying
HZ
Wu
Centre for Vascular Research, UNSW, Sydney, Australia.
Kwok Leung
KL
Ong
Centre for Healthy Brain and Ageing, School of Psychiatry, UNSW, Sydney, Australia.|Primary Dementia Collaborative Research Centre, UNSW, Sydney, Australia.
Katrin
K
Seeher
Centre for Healthy Brain and Ageing, School of Psychiatry, UNSW, Sydney, Australia.|Mathematics and Statistics, Murdoch University, Perth, Australia.
Nicola J
NJ
Armstrong
Centre for Healthy Brain and Ageing, School of Psychiatry, UNSW, Sydney, Australia.
Anbupalam
A
Thalamuthu
Centre for Healthy Brain and Ageing, School of Psychiatry, UNSW, Sydney, Australia.|Primary Dementia Collaborative Research Centre, UNSW, Sydney, Australia.
Henry
H
Brodaty
Centre for Healthy Brain and Ageing, School of Psychiatry, UNSW, Sydney, Australia.|Primary Dementia Collaborative Research Centre, UNSW, Sydney, Australia.
Perminder
P
Sachdev
Centre for Healthy Brain and Ageing, School of Psychiatry, UNSW, Sydney, Australia.
Karen
K
Mather
D000544:Alzheimer Disease / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D016206:Databases, Bibliographic / Q000706:statistics & numerical data; D006801:Humans; D035683:MicroRNAs / Q000097:blood*
D015415:Biomarkers; D035683:MicroRNAs
Alzheimer’s disease; biomarkers; dementia; microRNAs; mild cognitive impairment