A Sex Perspective in Neurodegenerative Diseases: microRNAs as Possible Peripheral Biomarkers
Abstract
:1. Introduction
2. microRNAs as Possible Biomarkers in Neurodegenerative Diseases
3. MicroRNAs in the Brain: From Function to Gender Differences
4. Sex Differences in Neurodegenerative Diseases
5. Peripheral Sex-Related miRNAs and Neurodegenerative Diseases
5.1. Alzheimer’s Disease and Frontotemporal Dementia
5.2. Parkinson’s Disease
5.3. Amyotrophic Lateral Sclerosis
6. Conclusions and Futures Perspectives
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Studies | Country | Specimen | Participants | Sample Size | Age (Mean ± SD) | Sex (M/F) | |||
---|---|---|---|---|---|---|---|---|---|
Cases | Controls | Cases | Controls | Cases | Controls | ||||
Alzheimer’s Disease and Frontotemporal Dementia | |||||||||
[81] | Italy | Plasma | FTD/HC | 48 | 46 | 72 ± 8 | 73 ± 7 | 20 (42%)/28 (58%) | 18 (39%)/28 (61%) |
[87] | USA, Germany | Blood | AD MCI HC/OND | 145 AD 38 MCI | 214 HC 68 OND | 72.9 ± 9.8 71.6 ± 6.2 | 68.9 ± 7.8 57 ± 18.7 | 76 (52%)/69 (47%) AD 18 (47%)/20 (53%)MCI | 103 (48%)/111 (52%) HC 23 (34%)/45 (66%) OND |
[84] | Germany | CSF, Serum | FTD/AD/HC | 96 FTD 95 AD | 82 | 65 ± 9.2 65 ± 9.3 | 64 ± 11.3 | 78 (81%)/18 (19%) FTD 69 (73%)/26 (27%) AD | 58 (71%)/24 (29%) |
[83] | Italy | Plasma | FTD/AD/HC | 54 FTD 20 AD | 53 | 70.3 ± 8.8 71.3 ± 8 | 71.6 ± 7.3 | 19 (35%)/35 (65%) FTD 10 (50%)/10 (50%) AD | 20 (38%)/33 (62%) |
[88] | Spain | Plasma | AD/PAD HC | 36 AD 36 PAD | 36 | 68.1 68.9 | 66.64 | 15 (42%)/21 (58%) AD 18 (50%)/18 (50%) PAD | 16 (44%)/20 (56%) |
[86] | Italy | Serum CSF | AD/FTD NINDC/INDC | 22 AD 10 FTD | 18NINDC 8 INDC | 72.7 ± 0.6 69.4 ± 0.6 | 68.8± 0.71 66.5± 0.22 | 8 (36%)/14 (64%) AD 2 (20%)/8 (80%) FTD | 13 (72%)/5 (28%) NINDC 0 (0%)/8 (100%) INDC |
Mild Cognitive Impairment (MCI) | |||||||||
[82] | Spain | Plasma | MCI/AD/HC | 30 MCI 35 AD | 31 | 76.8 ± 4.0 84.6 ± 3.5 | 75 ± 4.7 | 13 (43%)/17 (57%) MCI 14 (40%)/21 (60%) AD | 17 (55%)/14 (45%) |
[85] | Spain | Plasma | MCI/AD/HC | 26 MCI 56 AD | 14 | 72 ± 8.5 77.8 ±6.7 | 68.3± 8.99 | 10 (38%)/16 (62%) MCI 15 (27%)/41 (73%) AD | 7 (50%)/7 (50%) |
[90] | USA | Plasma | MCI/HC | 50 | 50 | 68.2 | 65.1 | 21 (42%)/29 (58%) | 26 (52%)/24 (48%) |
Parkinson’s disease | |||||||||
[92] | China | Saliva | PD/HC | 30 | 30 | 63.2 ± 10.2 | 59.7 ± 12.8 | 20 (67%)/10 (33%) | 16 (53%)/14 (47%) |
[89] | China | Plasma | PD/HC/NDC | 269 | 222 HC 176 NDC | 66.1 ± 0.61 | 66.2 ± 0.61 66.2 ± 0.74 | 157 (58%)/112 (42%) | 130 (59%)/92 (41%) HC 105 (60%)/71 (40%) NDC |
[91] | China | Serum | PD/HC | 80 | 80 | 64.0 ± 5.8 | 63.3 ± 5.4 | 48 (60%)/32 (40%) | 48 (60%)/32 (40%) |
Amotrophic Lateral Sclerosis | |||||||||
[93] | NR | Serum | ALS/HC | 12 | 12 | 57.0 ± 12.2 | 54.0 ± 14.5 | 6 (50%)/6 (50%) | 6 (50%)/6 (50%) |
Studies | Specimen | miRNA | Differences between Sexes | Possible Roles |
---|---|---|---|---|
Alzheimer’s Disease and Frontotemporal Dementia | ||||
[81] | Plasma | miR-206 miR-502-3p, miR-663a let-7e-5p | Downregulated in FTD vs. HC males (p < 0.05). Underexpressed both in males (p < 0.01; p < 0.1) and females (p < 0.1; p < 0.01). Downregulated in females with FTD (p < 0.05) | miR-206: synaptogenesis and neurogenesis. miR-502-3p: schizophrenia. miR-663a: inflammatory response, neuronal differentiation and development |
[87] | Blood | 10 miRNAs differentially expressed | No differences | Notch signaling pathway. |
[84] | CSF, Serum | 41 miRNAs differentially expressed: miR-103a-3p, miR-106a-5p, miR-1246 | No differences in expression level. AUC values better in males than females (miR-103a-3p: AUC = 0.80; miR-106a-5p: AUC = 0.80; miR-1246: AUC = 0.85) | miR-103a-3p and miR-106a-5p: involved in neuropathological processes by targeting LRP1, CDK5R1, DLG4 (Chang et al., 2017), APP, BACE1, PSEN1 (Yilmaz et al., 2016). miR1246: not yet studied |
[83] | Plasma | miR-127-3p | Downregulated in FTD with respect to AD or HC both in males (p < 0.0001; p < 0.05) and females (p < 0.001; p < 0.0001) | neuronal proliferation, differentiation and development |
[88] | Plasma | miR-34a-5p, miR-545-3p | No differences | miR-34a-5p: synaptic plasticity, glutamate receptors, potassium/sodium channels, antiapoptotic protein BCL-2 and SIRT1, inhibits pentose phosphate pathway in neurons and the mitochondrial functions. miR-545-3p targets the mRNA of the APOE receptor involved in Aβ clearance |
[86] | Serum, CSF | miR-125b, miR-6b | No differences | cell-cell communication |
Mild Cognitive Impairment | ||||
[82] | Plasma | miR-206 | No differences | neuronal survival, differentiation and signals transmission |
[85] | Plasma | miR-92a-1-3p, miR-181c-5p, miR-210-3p | No differences in expression levels. The ROCs show better diagnostic power in males (AUC = 0.957) than in females (AUC = 0.821) | synaptic plasticity, especially the glutammaergic ones |
[90] | Plasma | 6 miRNAs analysed: miR-132 sets miR-134 sets | No differences in expression levels. Better accuracy for male miR-132 sets of ROC (AUC = 0.99) compared with female (AUC = 0.98) and general ROCs (AUC better value = 0.97), and for female miR-134 sets of ROC (AUC = 0.96) compared with male (AUC = 0.90) and general ROCs (AUC better value = 0.93) | miR-132 and miR-134 family: Tau network and neuron growth |
Parkinson’s disease | ||||
[92] | Saliva | miR-874 | No differences | Synaptic function, morphogenesis, neurotransmitter regulation |
[89] | Plasma | miR-132 | Upregulated in male PD (p < 0.01). | Negative correlation with Nurr 1 |
[91] | Serum | miR-29a, miR-29b, miR-29c | Upregulated in female PD (p = 0.041; p = 0.0062; p = 0.0107). | Neurons survival, maturation, proliferation, synaptic plasticity, and morphogenesis |
Amotrophic Lateral Sclerosis | ||||
[93] | Serum | miR-206 | Upregulated in female ALS (p = 0.02) | synaptogenesis and neurogenesis |
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Piscopo, P.; Bellenghi, M.; Manzini, V.; Crestini, A.; Pontecorvi, G.; Corbo, M.; Ortona, E.; Carè, A.; Confaloni, A. A Sex Perspective in Neurodegenerative Diseases: microRNAs as Possible Peripheral Biomarkers. Int. J. Mol. Sci. 2021, 22, 4423. https://doi.org/10.3390/ijms22094423
Piscopo P, Bellenghi M, Manzini V, Crestini A, Pontecorvi G, Corbo M, Ortona E, Carè A, Confaloni A. A Sex Perspective in Neurodegenerative Diseases: microRNAs as Possible Peripheral Biomarkers. International Journal of Molecular Sciences. 2021; 22(9):4423. https://doi.org/10.3390/ijms22094423
Chicago/Turabian StylePiscopo, Paola, Maria Bellenghi, Valeria Manzini, Alessio Crestini, Giada Pontecorvi, Massimo Corbo, Elena Ortona, Alessandra Carè, and Annamaria Confaloni. 2021. "A Sex Perspective in Neurodegenerative Diseases: microRNAs as Possible Peripheral Biomarkers" International Journal of Molecular Sciences 22, no. 9: 4423. https://doi.org/10.3390/ijms22094423