A Plasma Circular RNA Profile Differentiates Subjects with Alzheimer’s Disease and Mild Cognitive Impairment from Healthy Controls
Abstract
:1. Introduction
2. Results
2.1. CircRNAs Profile by Microarray
2.2. Validation of Candidate circRNAs by qRT-PCR
2.3. ROC Showed Good Diagnostic Accuracy for All Six miRNAs Analyzed
2.4. CircRNA/miRNA Network
3. Discussion
4. Materials and Methods
4.1. Recruited Population
4.2. Sample Preparation
4.3. SIMOA analysis
4.4. Microarray Analysis
4.5. Quantitative Real-Time PCR Analysis
4.6. CircRNA-microRNA-mRNA Network
4.7. Statistical Analysis
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Pilot Study | Validation Study | ||||||
---|---|---|---|---|---|---|---|
HC | AD | HC | AD | MCI | |||
N. | 5 | 5 | 24 | 21 | 5 | ||
Sex (M/F) | 2/3 | 2/3 | p = n.s. | 10/14 | 9/12 | 3/2 | p = n.s. |
Age at the evaluation | 73.8 ± 4.3 | 74.4 ± 2.3 | p = n.s. | 69.9 ± 6.6 | 74.4 ± 6.1 | 70.0 ± 7.3 | p = n.s. |
Age at onset | - | 66.40 ± 6.5 | - | 70.6 ± 6.8 | 66.4 ± 6.5 | ||
MMSE | - | 21.4 ± 1.4 | - | 21.1 ± 1.7 | 25.6 ± 0.9 | ||
Aβ42/Aβ40 | NA | 0.04 ± 0.007 | 0.05 ± 0.001 | ||||
Total-tau | NA | 2.31± 1.9 | 2.98 ± 0.6 | ||||
p-tau | NA | 2.78 ± 0.5 | 2.37 ± 0.6 |
CircRNA | p-Value | FC (abs) | Regulation | Chrom. | Strand | circRNA_Type | Gene Symbol |
---|---|---|---|---|---|---|---|
hsa_circRNA_100837 | 0.0037 | 2.40 | up | chr11 | − | exonic | STX5 |
hsa_circRNA_100760 | 0.0042 | 2.23 | up | chr11 | − | exonic | DENND5A |
hsa_circRNA_403959 | 0.0051 | 2.23 | up | chr7 | − | exonic | BRAF |
hsa_circRNA_001131 | 0.0122 | 2.55 | up | chr2 | − | intronic | TLR5 |
hsa_circRNA_405788 | 0.0104 | 2.38 | up | chr19 | − | Exonic | CADM4 |
hsa_circRNA_050263 | 0.0155 | 2.19 | up | chr19 | − | exonic | ATP13A1 |
hsa_circRNA_003022 | 0.0180 | 2.14 | up | chr10 | − | exonic | PITRM1 |
hsa_circRNA_407191 | 0.0126 | 2.00 | up | chr9 | + | Sense overlapping | AL161626.1 |
hsa_circRNA_102750 | 0.0425 | 1.55 | up | chr2 | + | exonic | MEIS1 |
hsa_circRNA_105042 | 0.0128 | 1.90 | up | chrX | − | exonic | GAB3 |
hsa_circRNA_090183 | 0.0114 | 1.74 | up | chrX | + | exonic | PRRG1 |
hsa_circRNA_401844 | 0.0111 | 1.92 | up | chr17 | − | exonic | TUBD1 |
hsa_circRNA_080099 | 0.0073 | 1.66 | up | chr7 | − | exonic | MYO1G |
hsa_circRNA_004907 | 0.0316 | 1.60 | up | chr10 | + | exonic | ZEB1 |
hsa_circRNA_101222 | 0.0343 | 1.57 | up | chr13 | − | exonic | TPTE2 |
hsa_circRNA_002165 | 0.0340 | 1.60 | up | chr6 | − | exonic | SRPK1 |
hsa_circRNA_003022 | 0.0380 | 2.14 | up | chr10 | − | exonic | PITRM1 |
hsa_circRNA_003574 | 0.0104 | 1.88 | up | chr20 | + | exonic | GID8 |
hsa_circRNA_102885 | 0.0273 | 1.77 | up | chr2 | − | exonic | SATB2 |
hsa_circRNA_104671 | 0.0283 | 1.82 | up | chr8 | − | exonic | UBR5 |
hsa_circRNA_103618 | 0.0255 | 1.78 | up | chr4 | − | exonic | ARAP2 |
hsa_circRNA_104220 | 0.0109 | 1.67 | up | chr6 | + | exonic | PCMT1 |
hsa_circRNA_101752 | 0.0181 | 1.56 | up | chr16 | − | exonic | LOC100271836 |
hsa_circRNA_100759 | 0.0206 | 1.72 | up | chr11 | − | exonic | DENND5A |
hsa_circRNA_102049 | 0.0279 | 2.11 | down | chr17 | + | exonic | TADA2A |
hsa_circRNA_102619 | 0.0036 | 2.00 | down | chr2 | − | exonic | NOL10 |
hsa_circRNA_102645 | 0.0454 | 1.62 | down | chr2 | − | exonic | HADHA |
circRNA | Mean Value (∆Ct) | Standard Error | p_Values | p Values Adjusted | ||
---|---|---|---|---|---|---|
Hsa_circRNA_102049 | HC | 0.000737 | 0.000048 | HC/AD | <0.001 | <0.001 |
AD | 0.000404 | 0.000056 | HC/MCI | 0.355 | 0.474 | |
MCI | 0.000549 | 0.000077 | AD/MCI | 0.687 | 0.687 | |
Hsa_circRNA_050263 | HC | 0.000750 | 0.000093 | HC/AD | <0.001 | <0.001 |
AD | 0.002293 | 0.000120 | HC/MCI | <0.001 | <0.001 | |
MCI | 0.001945 | 0.000179 | AD/MCI | 0.494 | 0.668 | |
Hsa_circRNA_102619 | HC | 0.001418 | 0.000215 | HC/AD | 0.003 | 0.006 |
AD | 0.000585 | 0.000082 | HC/MCI | 0.430 | 0.548 | |
MCI | 0.000839 | 0.000228 | AD/MCI | 0.217 | 1.000 | |
Hsa_circRNA_403959 | HC | 0.001136 | 0.000114 | HC/AD | 0.013 | 0.026 |
AD | 0.001559 | 0.000116 | HC/MCI | <0.001 | <0.001 | |
MCI | 0.006260 | 0.003491 | AD/MCI | 0.001 | 0.001 | |
Hsa_circRNA_003022 | HC | 0.000295 | 0.000085 | HC/AD | 0.015 | 0.094 |
AD | 0.000695 | 0.000106 | HC/MCI | 0.015 | 0.016 | |
MCI | 0.000954 | 0.000227 | AD/MCI | 0.777 | 0.451 | |
Hsa_circRNA_100837 | HC | 0.000364 | 0.000039 | HC/AD | 0.389 | 0.072 |
AD | 0.001407 | 0.000555 | HC/MCI | 0.070 | 0.055 | |
MCI | 0.002972 | 0.002349 | AD/MCI | 0.513 | 1.000 |
Gene Name | Sequence (5′ to 3′) | Tm (°C) | Length of Product (bp) |
---|---|---|---|
hsa_circRNA_100837 | Forward:5′ AAGCAGTGGAAATTGAAGAGC3′ Reverse:5′ GCTGGCTTATTTGTCTGGATT3′ | 60 | 67 |
hsa_circRNA_403959 | Forward:5′ AGAAGACAGGAATCGAATGGACT3′ Reverse:5′ CAGGTAATGAGGCAGGGGG3′ | 60 | 96 |
hsa_circRNA_102619 | Forward:5′ GGGCATCTATTACATTCCATTCT3′ Reverse:5′ ATTATTCTCCGCAGCATCAGT3′ | 60 | 95 |
hsa_circRNA_003022 | Forward:5′ GATGAAGGGAGCGTTTACAGA3′ Reverse:5′ GGGAACAGATGTCACCTAGCA3′ | 60 | 192 |
hsa_circRNA_050263 | Forward:5′ CAAGCTCTCATCCATCCAGTG3′ Reverse:5′ ATGGGCGTACTCTCGTCCTC3′ | 60 | 73 |
hsa_circRNA_102049 | Forward:5′ CACAGCCATTCCATTTCACTACT3′ Reverse:5′ CAAAGCCACAGTCCATCACAG3′ | 60 | 105 |
β-actin | Forward:5′ GTGGCCGAGGACTTTGATTG3′ Reverse:5′ CCTGTAACAACGCATCTCATATT3′ | 60 | 73 |
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Piscopo, P.; Manzini, V.; Rivabene, R.; Crestini, A.; Le Pera, L.; Pizzi, E.; Veroni, C.; Talarico, G.; Peconi, M.; Castellano, A.E.; et al. A Plasma Circular RNA Profile Differentiates Subjects with Alzheimer’s Disease and Mild Cognitive Impairment from Healthy Controls. Int. J. Mol. Sci. 2022, 23, 13232. https://doi.org/10.3390/ijms232113232
Piscopo P, Manzini V, Rivabene R, Crestini A, Le Pera L, Pizzi E, Veroni C, Talarico G, Peconi M, Castellano AE, et al. A Plasma Circular RNA Profile Differentiates Subjects with Alzheimer’s Disease and Mild Cognitive Impairment from Healthy Controls. International Journal of Molecular Sciences. 2022; 23(21):13232. https://doi.org/10.3390/ijms232113232
Chicago/Turabian StylePiscopo, Paola, Valeria Manzini, Roberto Rivabene, Alessio Crestini, Loredana Le Pera, Elisabetta Pizzi, Caterina Veroni, Giuseppina Talarico, Martina Peconi, Anna Elisa Castellano, and et al. 2022. "A Plasma Circular RNA Profile Differentiates Subjects with Alzheimer’s Disease and Mild Cognitive Impairment from Healthy Controls" International Journal of Molecular Sciences 23, no. 21: 13232. https://doi.org/10.3390/ijms232113232