## 4 Results
### miRNA Pathway and Gene Ontology (GO) Analysis
\begin{table}
\begin{tabular}{c c c c} \hline \hline
**GO Category** & \(p\)**-Value** & **DEMi Involved** & **Genes Involved** \\ \hline respiratory electron & & & _ATPSE_ \\ transport chain & \(1.19\times 10^{-5}\) & hsa-miR-6501-5p & NDUIFB9 \\  & & & NDUIFB49 \\  & & & NDUIFS1 \\ \cline{3-4}  & & hsa-miR-143-3p & COX411 \\ \hline  & & hsa-miR-6501-5p & _ATPSE_ \\  & & hsa-miR-4433b-5p & _CALLM3_ \\ generation of precursor & 3.03 \(\times\) 10\({}^{-5}\) & & _NDUIFB9_ \\ metabolites and energy & & hsa-miR-143-3p & NDUIFB49 \\  & & & NDUIFS1 \\  & & & COX411 \\ \hline beta-amyloid metabolic process & 0.001017955 & hsa-miR-4433b-5p & _NCSTN_ \\  & & hsa-miR-143-3p & _PSEN1_ \\  & & & _BACE1_ \\ \hline calcium-mediated signalling & 0.001521237 & hsa-miR-6501-5p & _PP93 CA_ \\  & & hsa-miR-4433b-5p & _CALLM3_ \\  & & & hsa-miR-143-3p & _EIF2 AK3_ \\ \hline membrane protein & & hsa-miR-143-3p & _PSEN1_ \\ ectodomain proteolysis & 0.002220614 & hsa-miR-143-3p & _BACE1_ \\ \hline  & & & _NDUIFB9_ \\ mitochondrial inner membrane & 0.005473536 & hsa-miR-143-3p & _NCDIFB9_ \\  & & & _NDUIFA9_ \\  & & & _PSEN1_ \\  & & & _NCDIFS1_ \\  & & & COX411_ \\ \hline mitochondrial electron transport, & & & NDUIFB9 \\ NADH to ubiquinone & & & NDUIFB9 \\  & & & NDUIFA9 \\  & & & NDUIFB9 \\ NADH dehydrogenase & 0.01130008 & hsa-miR-143-3p & _NDUIFA9_ \\  & & & NDUIFS1_ \\ \hline mitochondrial respiratory & & & NDUIFB9 \\ chain complex I & 0.01133565 & hsa-miR-143-3p & _NDUIFA9_ \\  & & & NDUIFS1 \\ \hline amyloid precursor protein & & & \\ catabolic process & 0.0124875 & hsa-miR-4433b-5p & _NCSTN_ \\  & & & hsa-miR-143-3p & _PSEN1_ \\ \hline Notch-receptor processing & 0.01577116 & hsa-miR-4433b-5p & _NCSTN_ \\ \cline{3-4}  & & hsa-miR-143-3p & _PSEN1_ \\ \hline response to calcium ion & 0.01746326 & hsa-miR-6501-5p & _PP93 CA_ \\ \cline{3-4}  & & hsa-miR-4433b-5p & _CALLM3_ \\ \hline \hline \end{tabular}
\end{table} 
Table 4: GO terms associated with the miRNAs and the respective target genes. a strong association with the accumulation of \(A\beta\) and phosphorylated tau protein, the mechanisms involved in the pathogenesis of this disease are still uncertain and may be related to environmental, genetic, cultural, and other factors [2; 4]. The five common miRNAs identified (hsa-miR-6501-5p, hsa-miR-1296-5p, hsa-miR-1307-3p, hsa-miR-4433b-5p, and hsa-miR-143-3p), when the DEMis, using statistical (edgeR) and machine learning approaches were compared, were downregulated DEMis in edgeR (Table 1). Downregulated miRNAs often cause the upregulation of target genes, and vice versa, and as such, this finding may be related to the roles played by the miRNAs in suppressing mRNA expression [26]. Among these five commonly identified DEMis, only three DEMis ( hsa-miR-6501-5p, hsa-miR-4433b-5p, and hsa-miR-143-3p) were predicted to have target genes related to AD (see Table 2). Although the role of hsa-miR-6501-5p in AD is ambiguous, two target genes, _ATP5E_ and _PPP3 CA_, were predicted to be involved in AD-related pathways. Hsa-miR-4433, of which hsa-miR-4433b-5p is a member, has been identified as regulating glial cells and neuroimmune systems, indicating the participation of this miRNA in neurodegenerative disease [40]. HSA-miR-4433b-5p has also previously been associated with neurodegenerative diseases such as AD, Parkinson's disease (PD), and frontotemporal dementia (FTD) [41]. It is negatively correlated with lipids, where the formation of \(A\beta\) is involved in the cholesterol-metabolism regulation pathway [42]. In relation to AD, _GRIN2C_, _CALM3_, and _NCSTN_ are downstream target genes of hsa-miR-4433b-5p. Hsa-miR-143-3p has been suggested as a possible AD biomarker in review studies [43; 44]. In our study, hsa-miR-143-3p was downregulated in the plasma of AD patients, which is consistent with the findings seen in another study using an AD cell-culturing model [45]. The overexpression of hsa-miR-143-3p has been observed to attenuate tau phosphorylation, decrease _APP_ levels, and reduce \(A\beta\) accumulation [45].