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. 2019 Sep;56(9):6156-6167.
doi: 10.1007/s12035-019-1500-y. Epub 2019 Feb 8.

Systematic Review of miRNA as Biomarkers in Alzheimer's Disease

S Swarbrick  1 , N Wragg  1 , S Ghosh  1 , Alexandra Stolzing  2
Affiliations

Systematic Review of miRNA as Biomarkers in Alzheimer's Disease

S Swarbrick et al. Mol Neurobiol. 2019 Sep.

Abstract

Currently there are 850,000 people with Alzheimer's disease in the UK, with an estimated rise to 1.1 million by 2025. Alzheimer's disease is characterised by the accumulation of amyloid-beta plaques and hyperphosphorylated tau in the brain causing a progressive decline in cognitive impairment. Small non-coding microRNA (miRNA) sequences have been found to be deregulated in the peripheral blood of Alzheimer patients. A systematic review was conducted to extract all miRNA found to be significantly deregulated in the peripheral blood. These deregulated miRNAs were cross-referenced against the miRNAs deregulated in the brain at Braak Stage III. This resulted in a panel of 10 miRNAs (hsa-mir-107, hsa-mir-26b, hsa-mir-30e, hsa-mir-34a, hsa-mir-485, hsa-mir200c, hsa-mir-210, hsa-mir-146a, hsa-mir-34c, and hsa-mir-125b) hypothesised to be deregulated early in Alzheimer's disease, nearly 20 years before the onset of clinical symptoms. After network analysis of the 10 miRNAs, they were found to be associated with the immune system, cell cycle, gene expression, cellular response to stress, neuron growth factor signalling, wnt signalling, cellular senescence, and Rho GTPases.

Keywords: Alzheimer disease; Biomarkers; Brain; Peripheral blood; miRNA.

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Figures

Fig. 1
Fig. 1
Schematic of the Braak and Braak amyloid and tau stages during the progression of Alzheimer’s disease. Mild, moderate, and severe correspond to the density of amyloid/tau protein
Fig. 2
Fig. 2
Schematic showing the synthesis of miRNA
Fig. 3
Fig. 3
Forest plot showing the distribution of MMSE scores from 10 articles. Study ID: (1) Kiko (2014) [51], (2) Cheng (2014) [42], (3) Leidinger (2013) [41], (4) Zhu (2014) [59], (5) Kumar (2013) [48], (6) Geekiyanage (2012) [56], (7) Wang (2015) [61], (8) Tan (2014) [47], (9) Dong (2015) [57], and (10) Tan (2014) [44]
Fig. 4
Fig. 4
miRNA deregulated in peripheral blood experimentally found targets grouped into inflammation, apoptosis, amyloid, and tau signalling pathways
Fig. 5
Fig. 5
Schematic showing the number of miRNA deregulated in the different areas of the brain
Fig. 6
Fig. 6
Network diagram extracted from mirnet [91] miRNA’s (formula image) targets (formula image)
Fig. 7
Fig. 7
Roles of targets found in network analysis (Fig. 6)
See this image and copyright information in PMC

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