Abstract
Background: N6 adenosine methylation (m6A) is the most abundant internal RNA modification in eukaryotic cells. Dysregulation of m6A has been associated with the perturbations of cell proliferation and cell death in different diseases. However, the roles of m6A in the neurodegenerative process and cognitive dysfunction are unclear.Methods: We systematically investigated the molecular alterations of m6A regulators and their clinical relevance with cognitive dysfunctions using published datasets of Alzheimer's Disease (AD), vascular dementia, and mild cognitive impairment (MCI).Findings: The expressions of m6A regulators vary in different tissues and closely correlate with neurodegenerative pathways. We identified co-expressive m6A regulators SNRPG and SNRPD2 as potential biomarkers to predict transformation from MCI to AD. Moreover, we explored correlations between Apolipoprotein E4 and m6A methylations.Interpretation: Collectively, these findings suggest that m6A methylations as potential biomarkers and therapeutic targets for cognitive dysfunction.Funding: This work was supported by the National Natural Science Foundation of China (81871040) and the Shanghai Health System Talent Training Program (2018BR29).
Highlights
Alzheimer’s disease (AD) and vascular dementia (VD) are common neurocognitive disorders [1,2,3]
The gene-expression dataset with full clinical annotation was obtained from Gene Expression Omnibus (GEO), a publicly sponsored genomic database operated by the National Institutes of Health (NIH)
The expression profile of YTHDC2 mainly was enriched in the frontal lobe, while RBMX and FTO were in the temporal lobe, and IGF2BP3 was in the blood (Supplementary Figure 2A)
Summary
Alzheimer’s disease (AD) and vascular dementia (VD) are common neurocognitive disorders [1,2,3]. Mild cognitive impairment (MCI) is a transitional and reversible stage that can diverge to normal aging and neurocognitive disorder [8, 9]. Identifying biomarkers of neurocognitive disorders in the MCI stage is critical for early diagnosis and intervention [10]. Methods: We systematically investigated the molecular alterations of m6A regulators and their clinical relevance with cognitive dysfunctions using published datasets of Alzheimer's Disease (AD), vascular dementia, and mild cognitive impairment (MCI). Findings: The expressions of m6A regulators vary in different tissues and closely correlate with neurodegenerative pathways. We identified co-expressive m6A regulators SNRPG and SNRPD2 as potential biomarkers to predict transformation from MCI to AD. Interpretation: Collectively, these findings suggest that m6A methylations as potential biomarkers and therapeutic targets for cognitive dysfunction.
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