Table 1.
Downregulated miRNAs in AD subject, animal models of AD, and related cell lines and their functions in progression of AD.
| microRNA | Samples | Assessed cell line | Gene/protein interaction | Signaling pathway | Function | References |
|---|---|---|---|---|---|---|
| miR-129-5p | 90 male-specific pathogen-free (SPF) Sprague-Dawley (SD) rats | Hippocampal neuron cells of rat | SOX6 | - | Its upregulation represses apoptosis and inflammatory reactions and attenuates neural injury by targeting SOX6. | Zeng et al., 2019 |
| miR-200a-3p | Plasma samples from 7 patients with AD and 5 age-matched healthy individual, APP/PS1 mice, SAMP8, and SAMR1 mice | NB-1 | BACE1, PRKACB | - | Has neuroprotective effects, suppresses apoptosis, and decreases Aβ production through regulating expression of BACE1 and PRKACB | Wang et al., 2019b |
| miR-326 | APPswe/PS1d E9 double transgenic mouse | - | VAV1 | JNK signaling pathway | Its overexpression decreased neuronal apoptosis and Aβ accumulation and elevated viability of neuron cells by targeting VAV1. | He et al., 2020 |
| miR-98 | 70 Kunming mice | Hippocampal neuronal cells | HEY2 | Notch signaling pathway | Represses apoptosis of hippocampal neurons and shows enhanced survival of these cells by targeting HEY2 and inactivating the Notch signaling pathway | Chen et al., 2019 |
| miR-196a | 60 male Sprague-Dawley mice | HEK-293T | LRIG3 | PI3/Akt pathway | Its upregulation ameliorated cognitive decline, inhibited apoptosis, and increased survival of neurons by targeting LRIG3. | Yang et al., 2019a |
| miR-195 | Postmortem human brain tissues and CSF samples from AD patients and MCI subjects, Human ApoE4+/+ or ApoE3+/+ knock-in (KI) mice | Mouse primary neuron | synj1 | - | Its overexpression alleviated cognitive impairment and decreased Aβ deposition and tau hyper-phosphorylation. | Cao et al., 2020 |
| miR-195 | SAMP8 and SAMR1 mice | HEK293, N2a | BACE1 | - | Its overexpression reduced Aβ production through targeting BACE1. | Zhu et al., 2012 |
| miR-338-5p | Hippocampal tissue samples from patients with AD and normal subjects, 5XFAD transgenic (TG) mice | - | BACE1 | NF-κB signaling pathway | Its overexpression prevented Aβ formation, neuroinflammation, cognitive deficit and impaired learning ability by targeting BACE1. | Qian et al., 2019 |
| miR-338-5p | Male C57BL/6 mice and male APP/PS1 transgenic mice | Primary hippocampal neurons | BCL2L11 | - | Its overexpression prevented Aβ deposition, cognitive decline, and reduced apoptosis rate of neurons by targeting BCL2L11. | Li et al., 2020a |
| miR-133b | Serum samples from 105 AD patients and 98 control individuals | SH-SY5Y | EGFR | - | Its overexpression reduced apoptosis rate and improved cell viability. | Wang et al., 2019c |
| miR-124 | Male APP/PS1 transgenic mice | - | C1ql3 | - | Its overexpression increased angiogenesis and lowered the accumulation of Aβ and prevented memory decline and learning impairment. | Zhang et al., 2019 |
| miR-124-3p | - | N2a/APP695swe cells | Caveolin-1 | PI3K/Akt/GSK3β pathway | Its upregulation abated Tau hyperphosphorylation and cellular apoptosis by targeting Caveolin-1 and modulation of PI3K/Akt/GSK3β pathway. | Kang et al., 2017 |
| miR-101a | Plasma samples from 46 AD patients 60 healthy individuals, APPswe/ PS1ΔE9 transgenic mice | SH-SY5Y | MAPK1 | MAPK pathway | Regulates autophagy through targeting MAPK1 and modulating the MAPK pathway | Xiao et al., 2019 |
| miR-22 | Serum samples from 33 patients with AD and 30 healthy volunteers, APP/PS1 double transgenic mice | MG cells | GSDMD | - | Its overexpression suppressed secretion of inflammatory factors and pyroptosis also decreased GSDMD expression. | Han et al., 2020 |
| miR-34a | - | SH-SY5Y | Caspase-2 | - | Its upregulation suppressed neurotoxicity induced by Aβ through targeting Caspase-2. | Wang et al., 2019c |
| miR-34a | APP/PS1 transgenic mice | SH-SY5Y, primary cortical neuronal cells | cyclin D1 | - | Regulates apoptosis rate and neuronal cell cycle by targeting cyclin D1 | Modi et al., 2016 |
| miR-34a-5p miR-125b-5p |
Serum samples from 27 AD patients and 27 age-matched control individuals | N2a, MCN | BACE1 | - | Their overexpression ameliorated oxidative stress and apoptosis induced by Aβ through targeting BACE1. | Li et al., 2020b |
| miR-181a | APP/PS1 transgenic mice and male wild-type C67BL/6J mice | Murine brain pericytes | FOXO1 | - | Its overexpression alleviated cognitive decline, reduced accumulation of Aβ, and slowed pericyte loss by targeting FOXO1. | Wu et al., 2019 |
| miR-31 | Female AD triple-transgenic mice | HT-22, HEK293, SH-SY5Y | APP | - | Its overexpression reduced Aβ accumulation and alleviated neuropathology of AD and memory impairment. | Barros-Viegas et al., 2020 |
| miR-409-5p | APPswe/PS1ΔE9 double transgenic mice | PC12, Neuro2A, HEK293T | Plek | - | Its overexpression expression aggravated cell survival and differentiation and impaired neurite outgrowth by targeting Plek. | Guo et al., 2019 |
| miR-107 | CSF samples from 22 AD patients and 10 healthy controls | SH-SY5Y | FGF7 | FGFR2/PI3K/Akt pathway | Its upregulation reduced apoptosis and inflammation also elevated proliferation of SH-SY5Y through regulation of FGF7/FGFR2/PI3K/Akt Pathway induced by Aβ. | Chen et al., 2020a |
| miR-107 | - | hCMEC/D3, NHA, HBVP | Endophilin-1 | - | Its overexpression inhibited disruption of the blood–brain barrier induced by Aβ and alleviated impaired function of endothelial cells by targeting Endophilin-1. | Liu et al., 2016a |
| miR-107 miR-103 |
Post-mortem brain tissues from 12 AD patients and 12 age- and gender-matched control individuals | SK-N-BE, HEK-293 | CDK5R1 | - | Can be implicated in AD pathogenesis through regulation of CDK5R1 expression and consequently influencing p53 levels | Moncini et al., 2017 |
| miR-212 | Plasma sample from 31 AD patients and 31 control subjects | SH-SY5Y, IMR-32 | PDCD4 | PI3K/AKT signaling pathway | Reduces neurotoxicity of Aβ by targeting PDCD4 regulation of PI3K/AKT signaling pathway | Chang, 2020 |
| miR-433 | Serum samples from 118 AD patients and 62 healthy controls | SH-SY5Y, SK-N-SH | JAK2 | - | Its overexpression improved the viability of neurons by targeting JAK2. Its expression is associated with MMSE scores. | Wang and Zhang, 2020 |
| miR-132 | 70 SPF Sprague-Dawley rats | HEK 293T | MAPK1 | MAPK1 signal pathway | Suppresses oxidative stress and alleviated cognitive performance by targeting MAPK1 | Deng et al., 2020 |
| miR-132 | P301S Tau transgenic mice | Primary cortical and hippocampal neuron cultures | Rbfox1, GSK3β, EP300, Calpain 2 | - | Has neuroprotective effects including reduces neurotoxicity of Aβ and improves elongation of neurite and decreases neuronal death through targeting Rbfox1, GSK3β, EP300, and Calpain 2 | El Fatimy et al., 2018 |
| miR-132 miR-212 |
Human post-mortem brain tissues from 10 AD patients and 6 control subjects | Primary human neurons, SH-SY5Y | NOS1 | - | Low expression of miR-132 and miR-212 disrupted the balance of S-nitrosylation through modulation of NOS1 expression. | Wang et al., 2017 |
| miR-132 miR-212 |
Brain tissues from 29 AD patients and 16 controls | PC12, primary neurons | PTEN, FOXO3a, P300 | AKT signaling pathway | Regulates survival and apoptosis of neuronal cells through targeting PTEN, FOXO3a, and P300. | Wong et al., 2013 |
| miR-132 | Post-mortem brain tissues from AD patients, 3xTg-AD mice lacking the miR-132/212 cluster | Neuro2a, Neuro2a APPSwe/Δ9, HEK293T, HEK293-APPSwe | Sirt1 | - | Its deletion was associated with increased Aβ production and the establishment of amyloid plaque. | Hernandez-Rapp et al., 2016 |
| miR-132 | Brain tissues from AD patients and normal controls, APPPS1 mice | HEK293-APPswe | ITPKB | - | Regulates Aβ formation and TAU phosphorylation through targeting ITPKB and modulation of ERK1/2 and BACE1 activity. | Salta et al., 2016 |
| miR-9-5p | - | HT22 | GSK-3β | Nrf2/Keap1 signaling | Its overexpression caused a reduction in the apoptosis rate, oxidative stress, and prevention of mitochondrial malfunction by targeting GSK-3β. | Liu et al., 2020 |
| miR-377 | - | SH-SY5Y | CDH13 | - | Its upregulation enhanced cell proliferation and prevented occurrence apoptosis by targeting CDH13. | Liu et al., 2018 |
| miR-221 | Blood samples from 21 AD patients and 17 controls | SH-SY5Y | ADAM10 | - | Can be implicated in AD pathogenesis through regulation of ADAM10 expression | Manzine et al., 2018 |
| miR-186 | 72 male Sprague–Dawley (SD) rats | Hippocampal neuronal cells | IL2 | JAK-STAT signaling pathway | Its upregulation inhibited apoptosis and enhanced cell proliferation through targeting IL2 and regulation of the JAK-STAT signaling pathway. | Wu et al., 2018a |
| miR-330 | 14 C57 mice | Primary neuron cells obtained from mice | VAV1 | MAPK signaling pathway | Its overexpression reduced oxidative stress, ameliorated mitochondrial dysfunction, and decreased the generation of Aβ by targeting VAV1. | Han et al., 2018 |
| let-7f-5p | C57BL/6J-TgN (APP/PS1) ZLFILAS mice | Bone marrow mesenchymal stem cells | Caspase-3 | - | Its overexpression inhibited apoptosis induced by Aβ through targeting caspase-3. It also increased the survival rate of MSCs in mouse brain. | Shu et al., 2018 |
| miR-107 | 60 male C57 mice | - | - | - | Its overexpression alleviated spatial memory dysfunction, hippocampal long-term potentiation and prevented the elimination of pyramidal neurons induced resulted from neurotoxicity of Aβ. | Shu et al., 2018 |
| miRNA-140-5p | Post mortem brain tissues from 21 AD patients and 22 normal subjects | SHSY5Y, CHP212 | ADAM10, SOX2 | - | Is implicated in AD pathogenesis through targeting ADAM10 and its transcription factor SOX2 | Akhter et al., 2018 |
| miR-384 | Serum and CSF samples from 32 MCI patients, 45 AD patients, and 50 control individuals | SH-SY5Y, HEK293 | BACE-1, APP | - | Its overexpression decreased the expression of BACE-1 and APP so it can contribute to AD pathogenesis. | Liu et al., 2014b |
| miR-188-5p | Brain tissues from 5 AD patients and 3 controls, 5XFAD mice | Primary hippocampal neuron cells | - | - | Its overexpression alleviated cognitive dysfunction and memory loss also restored synaptic activity. | Lee et al., 2016 |
| miR-193b | Plasma and CSF samples from AD patients, MCI patients and control subjects, APP/PS1 double-transgenic | SH-SY5Y, HEK293 | APP | - | Its upregulation downregulated APP expression so it can be implicated in AD pathogenesis. | Liu et al., 2014a |
| miR-153 | APPswe/PSΔE9 mice | SH-SY5Y, HEK-293T, M17 | APP, APLP2 | - | Its overexpression downregulated expression APP and APLP2 so can be an important factor in the pathogenesis of AD. | Liang et al., 2012 |
| miR-153 | Brain tissues from 15 AD patients and 5 normal controls | HeLa, primary human fetal brain cultures | APP | - | Can be implicated in AD pathogenesis through targeting APP and reducing APP expression | Long et al., 2012 |
| miR-16 | SAMP8 mice, SAMR1 mice, and BALb/c mice | Neuroblastoma2a and NIH3T3 | APP | - | Its upregulation downregulated the expression of APP and consequently prevented APP accumulation. | Liu et al., 2012 |
| miR-339-5p | Frozen brain tissues from 20 AD patients and 5 controls | HeLa, U373 MG, human primary brain cultures | BACE1 | - | Can contribute to AD pathogenesis through targeting BACE1 | Long et al., 2014 |
| miR-214-3p | CSF samples from eight patients with sporadic AD and 8 age-matched healthy volunteers, SAMR1 and SAMP8 mice | Primary neurons obtained from SAMP8 mice, SH-SY5Y | Atg12 | - | Its upregulation decreased autophagy and apoptosis rate in neuronal cells and improved cognitive function through targeting Atg12. | Zhang et al., 2016a |
| miR-222 | APPswe/PSΔE9 mice | SH-SY5Y, HEK-293T | p27Kip1 | - | Regulates cell cycle by targeting p27Kip1 so can be involved in AD pathogenesis | Wang et al., 2015a |
| miR-29c | CSF samples from 30 AD patients and 30 age-matched controls | Primary hippocampal neurons | DNMT3 | - | Regulates neuronal proliferation by targeting DNMT3 and regulation of BDNF expression. | Yang et al., 2015 |
| miR-101 | - | Primary hippocampal neurons | APP | - | Its overexpression lead to decreased accumulation of Aβ through targeting APP. | Vilardo et al., 2010 |
| miR-181c | SAMP8 and SAMR1 mice | HT-22, HEK293A | crmp2 | - | Can be implicated in the pathogenesis of AD by targeting crmp2 and downregulation of crmp2 expression | Zhou et al., 2016 |
| miR-135b | Blood samples from 25 AD patients and 25 age-matched healthy individuals, | Primary hippocampal cells derived from SAMR1 mice | BACE1 | - | Its overexpression elevated cell proliferation and improved memory function and learning capacity by targeting BACE1. | Zhang et al., 2016b |