Table 2.
Upregulated miRNAs in AD subject, animal models of AD or related cell lines and their functions in progression of AD.
| microRNA | Samples | Assessed cell line | Gene/protein interaction | Signaling pathway | Function | References |
|---|---|---|---|---|---|---|
| miR-132 | Frozen human postmortem brain specimens from 10 patients with mild cognitive impairment, 10 patients with AD, and 10 controls | Human cortical neuron culture | GTDC-1 | - | Enhances neuronal apoptosis and Tau phosphorylation by targeting GTDC-1 | Liu and Zhang, 2019 |
| miR-30b | Human hippocampal tissues, C57BL/6J mice, and 5XFAD APP transgenic mice | NG108–15, HEK 293/293T | ephB2, sirt1, GluA2 | NF-κB signaling pathway | Disrupts cognitive and synaptic functions and its knockdown reverses this effect by targeting ephB2, sirt1, and GluA2 | Song et al., 2019 |
| miR-128 | APP/PSA/Tau triple transgenic mice and C57BL/6 mice | N2a cells | PPARγ | - | Its knockout suppressed AD development, Aβ production, and inflammatory reactions by targeting PPARγ. | Liu et al., 2019 |
| miR-128 | Plasma samples from 20 patients with AD and age and education-matched normal subjects | MCN, Neuro2a | PPAR-γ | - | Its inhibition abated neurotoxicity of Aβ through regulation of PPAR-γ and deactivated NF-κB. | Geng et al., 2018 |
| miR-7 | Postmortem human brains from AD patients and individuals without severe neurological and psychological disorders male C57BL/6 mice | N2a cell, BV-2 | INSR, IRS-2, IDE | Insulin signaling | Enhances extracellular Aβ and suppresses its clearance by regulating Insulin signaling through targeting INSR, IRS-2, and IDE | Fernández-de Frutos et al., 2019 |
| miR-592 | 54 Sprague-Dawley (SD) male rats established as an AD model | Astrocyte culture | KIAA0319 | Keap1/Nrf2/ARE signaling pathway | Its downregulation attenuated oxidative stress and enhanced cell survival through upregulation of KIAA0319. | Huang et al., 2020 |
| miR-425-5p | Postmortem brain tissue samples from | HEK293/tau | HSPB8 | - | Elevates apoptosis and tau phosphorylation through downregulation of HSPB8 | Yuan et al., 2020 |
| miR-425-5p miR-339-5p |
Blood samples (for PBMC) from 45 AD patients and 41 age- and gender-matched healthy controls | N2a/APPswe | BACE1 | - | Can be implicated in AD pathogenesis through modulating expression of BACE1 | Ren et al., 2016 |
| miR-25 | 30 male Kunming mice | Hippocampal neuronal cells | KLF2 | Nrf2 signaling pathway | Represses proliferation of hippocampal neuron cells and induced apoptosis in these cells by targeting KLF2 | Duan and Si, 2019 |
| miR-138 | - | SH-SY5Y | DEK | - | Increases apoptosis rate in SH-SY5Y cells by targeting DEK and downregulation of its expression | Miao et al., 2020 |
| miR-138q | - | N2a/APP, HEK293/tau | RARA | - | Can be implicated in the pathogenesis of AD through the promotion of tau phosphorylation by targeting RARA | Wang et al., 2015b |
| miR-149-5p | Plasma samples from 30 AD patients and 30 healthy controls | 293/APPsw | KAT8 | - | Can be implicated in AD pathology by targeting KAT8 to negatively regulate H4K16ac | Zhou et al., 2020 |
| miR-125b | Cerebral tissues from nine AD patients, eight patients with MCI, and 10 normal individuals | Neuronal cells obtained from human fatal cortical tissues | FOXQ1 | - | Promotes phosphorylation of Tau and apoptosis of neuronal cells by targeting FOXQ1 | Ma et al., 2017 |
| miR-125b | CSF samples from 24 AD patients and 24 healthy controls | Neuro2a APPSwe/Δ9 | - | - | Promotes cellular apoptosis, oxidative stress, and expression of inflammatory factors and suppressed cell proliferation by regulating SphK1 | Jin et al., 2018 |
| miR-125b | Brain tissue specimens 10 AD patients and 5 healthy controls, C57BL/6 wild-type mice | Primary hippocampal and cortical neuron obtained from embryonic day 19 rat | Bcl-W, DUSP6, PPP1CA | MAPK signaling | Its high expression resulted in increased tau phosphorylation through targeting Bcl-W, DUSP6 and PPP1CA. also its overexpression led to perished associative learning in mice. | Banzhaf-Strathmann et al., 2014 |
| miR-200b miR-200c |
Wild-type C57BL/6J mice and Tg2576 mice | PMNCs, SH-SY5Y | - | - | Transfection with miR-200b/miR-200c alleviated memory impairment and improved spatial learning through regulation of S6K1-mediated insulin signaling. | Higaki et al., 2018 |
| miR-200c | Plasma samples from 14 AD patients and 13 normal controls, APPswe/PS1ΔE9 double-transgenic mice | PC12 | PTEN | - | Its overexpression improved neuronal survival and neurite outgrowth by targeting PTEN. | Wu et al., 2016 |
| miR-10a | 50 male Sprague-Dawley (SD) rats | - | BDNF | BDNF-TrkB signaling pathway | Promotes apoptosis and cell growth arrest by targeting BDNF and inhibition of BDNF-TrkB signaling pathway | Wu et al., 2018b |
| miR-1908 | Blood samples from 20 AD patients and 20 age-matched control individuals | THP-1, U87 | ApoE | - | Disrupts clearance of Aβ by ApoE through downregulation of its expression | Wang et al., 2018 |
| miR-139 | SAMR1 and SAMP8 mice | Primary hippocampal cell | CB2 | - | Its overexpression improved memory function and learning ability by targeting CB2. | Tang et al., 2017 |
| miR-146a | - | SH-SY5Y | Lrp2 | Akt signaling pathway | Raised the rate of cellular apoptosis through targeting Lrp2 and inhibition of Akt signaling pathway | Wang et al., 2016 |
| miR-146a | Brain tissues from 17 AD patients, 5xFAD mice | SH-SY5Y | ROCK1 | ROCK1/PTEN pathway | Its inhibition decreased phosphorylation of tau proteins and improved memory function by modulating ROCK1 expression. | Wang et al., 2016 |
| miR-146a | Brain tissues from 36 AD patients and 30 control subjects | Primary human astroglial (HAG) cells, primary HNG | IRAK-1 | - | Targets IRAK-1 and downregulated its expression so caused a sustained inflammatory response | Cui et al., 2010 |
| miR-33 | APPsw/PSEN1Δ9 (APP/PS1) transgenic mice | N2a, N2a-APPsw, H4-APPsw | ABCA1 | - | Downregulates expression of ABCA1 and consequently impaired Aβ clearance | Kim et al., 2015 |
| miR-34c | C57 mice | Primary hippocampal neurons, N2a | VAMP2 | - | Its downregulation alleviated learning and memory dysfunction and synaptic impairment through targeting VAMP2. | Hu et al., 2015 |
| miR-26b | APP/PS1 double-transgenic mice | N2a, HEK293 | IGF-1 | - | Augments production of Aβ by targeting IGF-1 and its inhibition reversed these effects | Liu et al., 2016b |
| miR-98 | APP/PS1 mice | HEK293, N2a | IGF-1 | - | Its inhibition suppressed Aβ generation and tau phosphorylation by regulating the expression of IGF-1. | Hu et al., 2013 |
| miR-206 | Blood samples from 30 AD patients and 30 healthy controls | BV-2 | IGF-1 | - | Elevates inflammatory responses induced by LPS and promoted the release of Aβ from microglia cell through targeting IGF-1 | Xing et al., 2016 |
| miR-574 | APP/PS1 double transgenic mice and wild type mice | Primary hippocampal neurons obtained from mice | Nrn1 | - | Is involved in the regulation of synaptic activity and cognitive function through targeting Nrn1 | Li et al., 2015 |
| miR-26b | Postmortem brain tissues from 10 patients with MCI, 10 patients with AD, and eight controls | Primary cortical neurons obtained from Sprague Dawley rat | Rb1 | - | Promotes tau phosphorylation and cell cycle entry and consequently lead apoptosis by targeting Rb1 | Absalon et al., 2013 |
| miR-922 | - | SH-SY5Y, HEK-293T | UCHL1 | - | Enhances phosphorylation of tau proteins by targeting UCHL1 so contributed to AD pathogenesis | Zhao et al., 2014 |
| miR-485-3p | Serum samples from 89 AD patients and 62 healthy controls | SH-SY5Y, BV2 | AKT3 | - | Its knockdown promoted cell proliferation, inhibited apoptosis and neuroinflammation partly by targeting AKT3. Its expression has been associated with MMSE score, inflammatory response. | Yu et al., 2020 |