AbstractBackgroundMicroRNAs(miRNAs) form the most intensively characterised branch of non‐coding RNAs, with universal expression in a repertoire of biofluids and active regulatory roles in multiple biological pathways(Blount, Coursey, and Kocerha 2022). Therefore, any perturbance in miRNA expression produces pronounced biological effects, due to its pleiotropic nature(Blount, Coursey, and Kocerha 2022). A variety of miRNAs have been investigated in multiple dementia syndromes (Blount, Coursey, and Kocerha 2022). However, what remains to be evaluated is differential miRNA expression in dementia classified using the more toxic oligomeric amyloid beta(OAβ) as well as based on burden of cerebrovascular disease(CVD).MethodA cross‐sectional pilot study was conducted in a cohort of 24 research participants(Table 1), stratified on the basis of their plasma OAβ levels [Multimer Detection System based plasma OAβ analysis(PeopleBio Inc, South Korea)](Dominguez et al. 2022). T3 ‐ based MRI data was evaluated for CVD status ‐ White Matter Hyperintensity load, was scored using the Fazekas scale(Table 1). Blood plasma‐based expression profiling of 376 miRNAs was conducted using the ID3EAL™ PanoramiR miRNA Knowledge Panel(MiRXES Pte Ltd, Singapore) and normalised miRNA expression was defined via the delta‐delta(d) Ct method. MiRNA target interaction analyses was conducted using miRTarBase 9.0, revealing potential reactome pathways of interest(Huang et al. 2022).ResultMean age and MoCA scores are 60.05 and 25.42 respectively (Table 1). 10 miRNAs(upregulated : hsa‐miR‐42, hsa‐miR‐378c, hsa‐miR‐938; downregulated: hsa‐miR‐545‐3p, hsa‐miR‐449c‐5p, hsa‐miR‐657, hsa‐miR‐23c, hsa‐miR‐888‐5p, hsa‐miR‐599, hsa‐let‐7d‐5p) were significantly differentially expressed in OAβ positivity(Table 2). 6 miRNAs(upregulated: hsa‐miR‐513c‐5p, hsa‐miR‐592; downregulated: hsa‐miR‐98‐5p, hsa‐miR‐744‐5p, hsa‐let‐7d‐5p, hsa‐miR‐517‐5p were significantly differentially expressed in CVD(Table 2). Reactome pathways demonstrating putative biological relevance are the FOXO/p53 mediated transcriptional regulation (metabolism/senescence/neuronal genes),Caspase mediated inflammatory activation, Insulin/IGF‐1/PI3K/Akt/GSK3β mediated metabolic signalling, IL‐4/IL‐13 mediated immune(inflammatory) signalling, Nervous System/Axonal Development and WNT Signalling(Table 2).ConclusionFindings from this cross‐sectional pilot study, have revealed 16 miRNAs to be promising biomarker candidates within the OAβ positivity and CVD burden setting. Longitudinal study with larger sample size is on‐going to confirm and validate these findings.The authors wish to express their sincere gratitude to MiRXES Pte Ltd for their technical expertise and efforts towards the miRNA expression profiling and associated analyses.
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