Table 4.
MicroRNAs in human patients with AD or mild cognitive impairment.
| Reference | No. of Patients, Gender | Mean Age/Mean MMSE | Source | Screening Method/Validation Method | Dysregulated miRNAs | Functional Outcomes, Specificity and Sensitivity |
|---|---|---|---|---|---|---|
| Nagaraj et al. (2017) [111] | 7M/8F | 68.1 years/score 25.9 | Plasma without hemolysis and blood cells | RT-qPCR | Increased levels of miR486 and miR483-5p were the most significant indicators of MCI and AD. Also, upregulation of miR502-3p and miR-200a-3p in MCI and AD compared with NC was observed. | ROC indicated that miR483-5p and miR-502-3p are good tests to distinguish AD from NC, and MCI from NC (AUC > 0.9, specificity and sensitivity > 0.8, repeatedly, in both screening and validation studies). |
| Müller et al. (2016) [113] | 15M/22F | 73.1 years/score 24.8 | CSF | qPCR | Increased expression levels of miRNA-146a in MCI compared with NC were lost when confounding factors were considered. Similarly, increased expression levels of miRNA-27a, -125b, -146a in MCI compared with AD were lost after correcting for confounding factors. | After correcting for confounding factors, no differences in miRNA levels were found between AD, MCI and NC |
| Weinberg et al., (2015) [114] | 5M/5F | 82.9 years/score 28.0 | Frontal and interior temporal cortex obtained at postmortem (60% MCI as Braak stages III-VI) | Microarray/qPCR | miR-150 was upregulated in MCI, compared with NC. Also, two distinct clusters miR-212/miR-132 and miR-23a/miR-23b were significantly downregulated in MCI | SIFT1 mRNA levels were significantly upregulated by 40% in frontal cortex of MCI compared with AD and NC |
| Liu et al., (2018) [112] | 19M/17F, | 72.4 years/score 56.6 | CSF | RT-PCR | Let-7b was significantly increased in MCI compared with SMC. Let-7b expression in CD4+ lymphocyte population from MCI was higher than SMC. | Addition of let-7b improves diagnostic performance of Aβ40 and Aβ42, and of t-tau and p-tau |
| Kayano et al., (2016) [115] | 11M/12F, | 72.8 years/score 24.3 | Plasma | RT-qPCR | Differential correlation analysis was applied to the data set with 85 miRNAs. The 20 pairs of miRNAs which had the difference of correction coefficients > 0.8 were selected as biomarkers that distinguish MCI from NC | Two miRNA pairs miR-191/miR-101 and miR-103/miR-222 have the highest value AUC 0.96 and are good tests to distinguish MCI from NC. Also, miR-191 and miR-125b and miRN-590-5p have a high AUC > 0.95 |
AD = Alzheimer’s disease; MCI = mild cognitive impairment; NC = Normal control; M = Male; FT = Female; RT-qPCR = Quantitative reverse transcription PCR; CSF = Cerebrospinal fluid; MMSE = Mini-Mental State Examination.