An atlas of cortical circular RNA expression in Alzheimer disease brains demonstrates clinical and pathological associations
Open accessAbstract
Parietal cortex RNA-sequencing (RNA-seq) data were generated from individuals with and without Alzheimer disease (AD; n control = 13; n AD = 83) from the Knight Alzheimer Disease Research Center (Knight ADRC). Using this and an independent (Mount Sinai Brain Bank (MSBB)) AD RNA-seq dataset, cortical circular RNA (circRNA) expression was quantified in the context of AD. Significant associations were identified between circRNA expression and AD diagnosis, clinical dementia severity and neuropathological severity. It was demonstrated that most circRNA-AD associations are independent of changes in cognate linear messenger RNA expression or estimated brain cell-type proportions. Evidence was provided for circRNA expression changes occurring early in presymptomatic AD and in autosomal dominant AD. It was also observed that AD-associated circRNAs co-expressed with known AD genes. Finally, potential microRNA-binding sites were identified in AD-associated circRNAs for miRNAs predicted to target AD genes. Together, these results highlight the importance of analyzing non-linear RNAs and support future studies exploring the potential roles of circRNAs in AD pathogenesis.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
An association between circRNA expression and AD has been established.
“A very recent study has established an association between circRNA expression and AD [620].”
From Molecular and cellular mechanisms underlying the pathogenesis of Alzheimer’s disease (2020) · cites this paper as [620]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2
Love, M. I., Huber, W., & Anders, S. (2014) · Genome Biology · doi:10.1186/s13059-014-0550-8 · Cited by 95,106 · cited 14× · see citing works
“Results for circRNA correlation with mean number of plaques were consistent with the other traits in all MSBB cortical regions (Supplementary Tables 36–39, Supplementary Figure 7 and Supplementary Results).”
InfluentialSTAR: ultrafast universal RNA-seq aligner
Dobin, A., Davis, C. A., Schlesinger, F., Drenkow, J., Zaleski, C., Jha, S., Batut, P., Chaisson, M., & Gingeras, T. R. (2013) · Bioinformatics · doi:10.1093/bioinformatics/bts635 · Cited by 51,709 · cited 12× · see citing works
“Results for circRNA correlation with mean number of plaques were consistent with the other traits in all MSBB cortical regions (Supplementary Tables 36–39, Supplementary Figure 7 and Supplementary Results).”
InfluentialWGCNA: an R package for weighted correlation network analysis
Langfelder, P., & Horvath, S. (2008) · BMC Bioinformatics · doi:10.1186/1471-2105-9-559 · Cited by 27,252 · see citing works
Second-generation PLINK: rising to the challenge of larger and richer datasets
Chang, C. C., Chow, C. C., Tellier, L. C., Vattikuti, S., Purcell, S. M., & Lee, J. J. (2015) · Gigascience · doi:10.1186/s13742-015-0047-8 · Cited by 12,709 · cited 13× · see citing works
“Results for circRNA correlation with mean number of plaques were consistent with the other traits in all MSBB cortical regions (Supplementary Tables 36–39, Supplementary Figure 7 and Supplementary Results).”
InfluentialSelf-citationSalmon provides fast and bias-aware quantification of transcript expression
Patro, R., Duggal, G., Love, M. I., Irizarry, R. A., & Kingsford, C. (2017) · Nature Methods · doi:10.1038/nmeth.4197 · Cited by 12,700 · see citing works
The Clinical Dementia Rating (CDR): Current version and scoring rules
Morris, J. C. (1993) · Neurology · doi:10.1212/wnl.43.11.2412-a · Cited by 9,882 · see citing works
Self-citationCircular RNAs are a large class of animal RNAs with regulatory potency
Memczak, S., Jens, M., Elefsinioti, A., Torti, F., Krueger, J., Rybak, A., Maier, L., Mackowiak, S. D., Gregersen, L. H., Munschauer, M., et al. (2013) · Nature · doi:10.1038/nature11928 · Cited by 7,990 · see citing works
Natural RNA circles function as efficient microRNA sponges
Hansen, T. B., Jensen, T. I., Clausen, B. H., Bramsen, J. B., Finsen, B., Damgaard, C. K., & Kjems, J. (2013) · Nature · doi:10.1038/nature11993 · Cited by 7,985 · see citing works
Predicting effective microRNA target sites in mammalian mRNAs
Agarwal, V., Bell, G. W., Nam, J.-W., & Bartel, D. P. (2015) · eLife · doi:10.7554/elife.05005 · Cited by 7,318 · see citing works
The International HapMap Project
†The International HapMap Consortium, Genotyping centres: Baylor College of Medicine and ParAllele BioScience, Gibbs, R. A., Belmont, J. W., Hardenbol, P., Willis, T. D., Yu, F., Chinese HapMap Consortium, Yang, H., Ch'ang, L.-Y., et al. (2003) · Nature · doi:10.1038/nature02168 · Cited by 6,057 · see citing works
Self-citationMirra, S. S., Heyman, A., McKeel, D., Sumi, S. M., Crain, B. J., Brownlee, L. M., Vogel, F. S., Hughes, J. P., Belle, G. V., Berg, L., et al. (1991) · Neurology · doi:10.1212/wnl.41.4.479 · Cited by 4,961 · see citing works
GENCODE: The reference human genome annotation for The ENCODE Project
Harrow, J., Frankish, A., Gonzalez, J. M., Tapanari, E., Diekhans, M., Kokocinski, F., Aken, B. L., Barrell, D., Zadissa, A., Searle, S., et al. (2012) · Genome Research · doi:10.1101/gr.135350.111 · Cited by 4,585 · cited 4× · see citing works
“In short, we generated a quasi-mapping index using the primary assembly of the human reference genome, GRCh38, and the GENCODE v26 28 comprehensive gene annotation.”
InfluentialFunctional mapping and annotation of genetic associations with FUMA
Watanabe, K., Taskesen, E., van Bochoven, A., & Posthuma, D. (2017) · Nature Communications · doi:10.1038/s41467-017-01261-5 · Cited by 4,083 · cited 2× · see citing works
“Co-expression module enrichment for AD-related pathways was determined using a one-tailed hypergeometric test performed by FUMA software 60 .”
Braak, H., Alafuzoff, I., Arzberger, T., Kretzschmar, H., & Del Tredici, K. (2006) · Acta Neuropathologica · doi:10.1007/s00401-006-0127-z · Cited by 3,172 · see citing works
Scheltens, P., Blennow, K., Breteler, M. M. B., de Strooper, B., Frisoni, G. B., Salloway, S., & Van der Flier, W. M. (2016) · The Lancet · doi:10.1016/s0140-6736(15)01124-1 · Cited by 3,125 · see citing works
Self-citationcircRNA biogenesis competes with pre-mRNA splicing
Ashwal-Fluss, R., Meyer, M., Pamudurti, N. R., Ivanov, A., Bartok, O., Hanan, M., Evantal, N., Memczak, S., Rajewsky, N., & Kadener, S. (2014) · Molecular Cell · doi:10.1016/j.molcel.2014.08.019 · Cited by 3,083 · see citing works
RSeQC: quality control of RNA-seq experiments
Wang, L., Wang, S., & Li, W. (2012) · Bioinformatics · doi:10.1093/bioinformatics/bts356 · Cited by 2,813 · see citing works
Relative Importance for Linear Regression in <i>R</i> : The Package <b>relaimpo</b>
Grömping, U. (2006) · Journal of Statistical Software · doi:10.18637/jss.v017.i01 · Cited by 2,615 · cited 3× · see citing works
“2.3 38 .”
InfluentialDiagnosis of Alzheimer's Disease
Khachaturian, Z. S. (1985) · Archives of Neurology · doi:10.1001/archneur.1985.04060100083029 · Cited by 2,499 · see citing works
Salzman, J., Gawad, C., Wang, P. L., Lacayo, N. J., & Brown, P. O. (2012) · PLoS ONE · doi:10.1371/journal.pone.0030733 · Cited by 2,457 · see citing works
Self-citationCircular RNAs in the Mammalian Brain Are Highly Abundant, Conserved, and Dynamically Expressed
Rybak-Wolf, A., Stottmeister, C., Glažar, P., Jens, M., Pino, N., Giusti, S., Hanan, M., Behm, M., Bartok, O., Ashwal-Fluss, R., et al. (2015) · Molecular Cell · doi:10.1016/j.molcel.2015.03.027 · Cited by 2,423 · see citing works
Circular RNA is enriched and stable in exosomes: a promising biomarker for cancer diagnosis
Li, Y., Zheng, Q., Bao, C., Li, S., Guo, W., Zhao, J., Chen, D., Gu, J., He, X., & Huang, S. (2015) · Cell Research · doi:10.1038/cr.2015.82 · Cited by 2,210 · see citing works
Circ-ZNF609 is a circular RNA that can be translated and functions in myogenesis
Legnini, I., Di Timoteo, G., Rossi, F., Morlando, M., Briganti, F., Sthandier, O., Fatica, A., Santini, T., Andronache, A., Wade, M., et al. (2017) · Molecular Cell · doi:10.1016/j.molcel.2017.02.017 · Cited by 2,173 · cited 2× · see citing works
“Much is still unknown regarding circRNA biology; for example, it was only recently demonstrated that circRNAs can be translated in vivo 13,14 .”
The Biogenesis, Functions, and Challenges of Circular RNAs
Li, X., Yang, L. C., & Chen, L. (2018) · Molecular Cell · doi:10.1016/j.molcel.2018.06.034 · Cited by 2,043 · see citing works
circBase: a database for circular RNAs
Glažar, P., Papavasileiou, P., & Rajewsky, N. (2014) · RNA · doi:10.1261/rna.043687.113 · Cited by 1,934 · cited 13× · see citing works
“In our discovery, parietal cortex dataset, the majority (5,090/7,450) of the backsplice junctions we identified using this calling and filtering approach have been previously identified using a different calling algorithm in an independent analysis of healthy parietal cortex tissue 10,55 .”
InfluentialPamudurti, N. R., Bartok, O., Jens, M., Ashwal-Fluss, R., Stottmeister, C., Ruhe, L., Hanan, M., Wyler, E., Perez-Hernandez, D., Ramberger, E., et al. (2017) · Molecular Cell · doi:10.1016/j.molcel.2017.02.021 · Cited by 1,810 · see citing works
Integrated Systems Approach Identifies Genetic Nodes and Networks in Late-Onset Alzheimer’s Disease
Zhang, B., Gaiteri, C., Bodea, L.-G., Wang, Z., McElwee, J., Podtelezhnikov, A. A., Zhang, C., Xie, T., Tran, L., Dobrin, R., et al. (2013) · Cell · doi:10.1016/j.cell.2013.03.030 · Cited by 1,657 · see citing works
Transcriptional Regulation and Its Misregulation in Disease
Lee, T. I., & Young, R. A. (2013) · Cell · doi:10.1016/j.cell.2013.02.014 · Cited by 1,588 · see citing works
Expanded identification and characterization of mammalian circular RNAs
Guo, J. U., Agarwal, V., Guo, H., & Bartel, D. P. (2014) · Genome biology · doi:10.1186/s13059-014-0409-z · Cited by 1,578 · see citing works
Loss of a mammalian circular RNA locus causes miRNA deregulation and affects brain function
Piwecka, M., Glažar, P., Hernandez-Miranda, L. R., Memczak, S., Wolf, S. A., Rybak-Wolf, A., Filipchyk, A., Klironomos, F., Cerda Jara, C. A., Fenske, P., et al. (2017) · Science · doi:10.1126/science.aam8526 · Cited by 1,210 · see citing works
Neural circular RNAs are derived from synaptic genes and regulated by development and plasticity
You, X., Vlatkovic, I., Babic, A., Will, T., Epstein, I., Tushev, G., Akbalik, G., Wang, M., Glock, C., Quedenau, C., et al. (2015) · Nature Neuroscience · doi:10.1038/nn.3975 · Cited by 1,149 · see citing works
Westholm, J. O., Miura, P., Olson, S., Shenker, S., Joseph, B. J., Sanfilippo, P., Celniker, S., Graveley, B. R., & Lai, E. C. (2014) · Cell Reports · doi:10.1016/j.celrep.2014.10.062 · Cited by 1,001 · see citing works
Circular RNAs: analysis, expression and potential functions
Barrett, S. P., & Salzman, J. (2016) · Development · doi:10.1242/dev.128074 · Cited by 859 · see citing works
Circular RNA (circRNA) in Alzheimer’s disease (AD)
Lukiw, W. J. (2013) · Frontiers in Genetics · doi:10.3389/fgene.2013.00307 · Cited by 636 · cited 13× · see citing works
“Results for circRNA correlation with mean number of plaques were consistent with the other traits in all MSBB cortical regions (Supplementary Tables 36–39, Supplementary Figure 7 and Supplementary Results).”
InfluentialLiang, W. S., Reiman, E. M., Valla, J., Dunckley, T., Beach, T. G., Grover, A., Niedzielko, T. L., Schneider, L. E., Mastroeni, D., Caselli, R., et al. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0709259105 · Cited by 585 · see citing works
Self-citationBateman, R. J., Aisen, P. S., De Strooper, B., Fox, N. C., Lemere, C. A., Ringman, J. M., Salloway, S., Sperling, R. A., Windisch, M., & Xiong, C. (2010) · Alzheimer's Research & Therapy · doi:10.1186/alzrt59 · Cited by 573 · cited 4× · see citing works
“Brain hypometabolism has also been demonstrated in PSEN1 mutation-driven ADAD 48,49 and circHOMER1 contains multiple predicted bindings sites for miR-651, an miRNA predicted to target PSEN1 and PSEN2 42 .”
InfluentialSelf-citationWang, M., Beckmann, N. D., Roussos, P., Wang, E., Zhou, X., Wang, Q., Ming, C., Neff, R., Ma, W., Fullard, J. F., et al. (2018) · Scientific Data · doi:10.1038/sdata.2018.185 · Cited by 502 · cited 5× · see citing works
“From these libraries, rRNA-depleted 101nt single-end, and non-stranded RNA-seq data was generated via an Illumina HiSeq 2500 (Illumina, San Diego, USA) 26 .”
InfluentialSelf-citationSpatio-temporal regulation of circular RNA expression during porcine embryonic brain development
Venø, M. T., Hansen, T. B., Venø, S. T., Clausen, B. H., Grebing, M., Finsen, B. R., Holm, I. E., & Kjems, J. (2015) · Genome biology · doi:10.1186/s13059-015-0801-3 · Cited by 475 · cited 1× · see citing works
“Brain circRNAs are also regulated during development 5,10,12 and in response to neuronal excitation 8 .”
Liang, D., Tatomer, D. C., Luo, Z., Wu, H., Yang, L. C., Chen, L., Cherry, S. R., & Wilusz, J. E. (2017) · Molecular Cell · doi:10.1016/j.molcel.2017.10.034 · Cited by 435 · cited 1× · see citing works
“In the brain, circRNA expression can occur independently of linear transcript expression 8 , and may be a gene’s most highly expressed isoform 3,8,10,11 .”
Raj, T., Li, Y. I., Wong, G., Humphrey, J., Wang, M., Ramdhani, S., Wang, Y.-C., Ng, B., Gupta, I., Haroutunian, V., et al. (2018) · Nature Genetics · doi:10.1038/s41588-018-0238-1 · Cited by 430 · see citing works
Efficient Test and Visualization of Multi-Set Intersections
Wang, M., Zhao, Y., & Zhang, B. (2015) · Scientific Reports · doi:10.1038/srep16923 · Cited by 395 · see citing works
A map of human circular RNAs in clinically relevant tissues
Maass, P. G., Glažar, P., Memczak, S., Dittmar, G. A. G., Hollfinger, I., Schreyer, L., Sauer, A. V., Toka, O., Aiuti, A., Luft, F. C., et al. (2017) · Journal of Molecular Medicine · doi:10.1007/s00109-017-1582-9 · Cited by 388 · see citing works
Bai, Y., Zhang, Y., Han, B., Yang, L., Chen, X., Huang, R., Wu, F., Chao, J., Liu, P., Hu, G., et al. (2017) · Journal of Neuroscience · doi:10.1523/jneurosci.1348-17.2017 · Cited by 379 · see citing works
Specific identification and quantification of circular RNAs from sequencing data
Cheng, J., Metge, F., & Dieterich, C. (2015) · Bioinformatics · doi:10.1093/bioinformatics/btv656 · Cited by 372 · see citing works
CircRNA accumulation in the aging mouse brain
Gruner, H. N., Cortés-López, M., Cooper, D. A., Bauer, M. J., & Miura, P. (2016) · Scientific Reports · doi:10.1038/srep38907 · Cited by 366 · see citing works
Multiscale Embedded Gene Co-expression Network Analysis
Song, W., & Zhang, B. (2015) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1004574 · Cited by 357 · cited 3× · see citing works
“3.6 39 .”
InfluentialExpression of Novel Alzheimer’s Disease Risk Genes in Control and Alzheimer’s Disease Brains
Karch, C. M., Jeng, A. T., Nowotny, P., Cady, J., Cruchaga, C., & Goate, A. M. (2012) · PLoS ONE · doi:10.1371/journal.pone.0050976 · Cited by 328 · see citing works
Self-citation(2006) · PubMed · Cited by 269 · see citing works
Measure transcript integrity using RNA-seq data
Wang, L., Nie, J. J., Sicotte, H., Li, Y., Eckel‐Passow, J. E., Dasari, S., Vedell, P. T., Barman, P., Wang, L., Weinshiboum, R., et al. (2016) · BMC Bioinformatics · doi:10.1186/s12859-016-0922-z · Cited by 256 · cited 16× · see citing works
“For example, the effect size Pearson correlation for the 31 discovery analysis CDR-associated circRNAs obtained after substituting RIN for TIN is 0.99 (p-value: 5.43×10 −26 ).”
InfluentialUnderstanding Alzheimer Disease at the Interface between Genetics and Transcriptomics
Verheijen, J., & Sleegers, K. (2018) · Trends in Genetics · doi:10.1016/j.tig.2018.02.007 · Cited by 189 · see citing works
Krishnan, K. C., Kurt, Z., Barrere‐Cain, R., Sabir, S., Das, A., Floyd, R. R., Vergnes, L., Zhao, Y., Che, N., Charugundla, S., et al. (2018) · Cell Systems · doi:10.1016/j.cels.2017.12.006 · Cited by 149 · see citing works
Brain and Bannister's Clinical Neurology, 7th Ed.
Cole, M. (1993) · Neurology · doi:10.1212/wnl.43.1_part_1.241-a · Cited by 126 · see citing works
MiR‐136 promotes apoptosis of glioma cells by targeting AEG‐1 and Bcl‐2
Yang, Y., Wu, J., Guan, H., Cai, J., Fang, L., Li, J., & Li, M. (2012) · FEBS Letters · doi:10.1016/j.febslet.2012.08.003 · Cited by 121 · see citing works
Executive deficits are related to the inferior frontal junction in early dementia
Schroeter, M. L., Vogt, B., Frisch, S., Becker, G., Barthel, H., Mueller, K., Villringer, A., & Sabri, O. (2011) · Brain · doi:10.1093/brain/awr311 · Cited by 116 · see citing works
ciRS-7 exonic sequence is embedded in a long non-coding RNA locus
Barrett, S. P., Parker, K. R., Horn, C., Mata, M. A., & Salzman, J. (2017) · PLoS Genetics · doi:10.1371/journal.pgen.1007114 · Cited by 98 · see citing works
Perkins, M., Wolf, A. B., Chavira, B., Shonebarger, D., Meckel, J. P., Leung, L., Ballina, L. E., Ly, S., Saini, A., Jones, T. B., et al. (2016) · Journal of Alzheimer s Disease · doi:10.3233/jad-151205 · Cited by 74 · cited 1× · see citing works
“For example, circHOMER1, which was significantly associated with all three AD traits, co-expressed with linear genes involved in AD and oxidative phosphorylation, perhaps suggesting a role for this circRNA in brain hypometabolism associated with AD 45–47 .”
Distinct pattern of hypometabolism and atrophy in preclinical and predementia Alzheimer's disease
Kljajević, V., Grothe, M. J., Ewers, M., & Teipel, S. J. (2014) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2014.04.006 · Cited by 65 · see citing works
The Dominantly Inherited Alzheimer Network (DIAN), Li, Z., Del-Aguila, J. L., Dube, U., Budde, J., Martinez, R., Black, K., Xiao, Q., Cairns, N. J., Dougherty, J. D., et al. (2018) · Genome Medicine · doi:10.1186/s13073-018-0551-4 · Cited by 56 · cited 5× · see citing works
“…analyses 38 to assess the contribution of circRNA expression to the variation in AD quantitative traits: CDR and Braak score compared to two known contributors: number of APOE4 alleles (APOE4) – the most common genetic risk factor for AD 16 – and the estimated proportion of neurons (EstNeuron) 34 .”
InfluentialSelf-citationPine, P. S., Munro, S. A., Parsons, J., McDaniel, J., Lucas, A. B., Lozach, J., Myers, T. G., Su, Q., Jacobs-Helber, S. M., & Salit, M. (2016) · BMC Biotechnology · doi:10.1186/s12896-016-0281-x · Cited by 50 · see citing works
Smith, R. A., Wibom, M., Olsson, T. G., Hägerström, D., Jögi, J., Rabinovici, G. D., & Hansson, O. (2016) · Journal of Alzheimer s Disease · doi:10.3233/jad-151004 · Cited by 30 · see citing works
Template switching causes artificial junction formation and false identification of circular RNAsPreprint
Tang, C., Yu, T., Xie, Y., et al. (2018) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/259556 · Cited by 7 · cited 2× · see citing works
“…Figure 9 and Supplementary Tables 50–51) and when analyzing the other MSBB tissues for contribution of circRNAs to variation in CDR (Supplementary Tables 52–54), Braak score (Supplementary Tables 55–57), and mean number of plaques (Supplementary Tables 58–61 and Supplementary results).”
Flagged first, then by citations
1 of the 63 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
The expanding regulatory mechanisms and cellular functions of circular RNAs
Chen, L. (2020) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-020-0243-y · Cited by 1,714 · see citing works
Circular RNAs: Characterization, cellular roles, and applications
Liu, C., & Chen, L. (2022) · Cell · doi:10.1016/j.cell.2022.04.021 · Cited by 1,084 · see citing works
Molecular and cellular mechanisms underlying the pathogenesis of Alzheimer’s disease
Guo, T., Zhang, D., Zeng, Y., Huang, T. Y., Xu, H., & Zhao, Y. (2020) · Molecular Neurodegeneration · doi:10.1186/s13024-020-00391-7 · Cited by 994 · see citing works
“A very recent study has established an association between circRNA expression and AD [620].”
BackgroundNon-coding RNAs in disease: from mechanisms to therapeutics
Németh, K., Bayraktar, R., Ferracin, M., & Călin, G. A. (2023) · Nature Reviews Genetics · doi:10.1038/s41576-023-00662-1 · Cited by 935 · see citing works
“Overall, despite clear evidence of aberrant expression of circRNAs in neurological disorders 169–171 , the functional significance of these alterations remains to be thoroughly investigated.”
Specific expression and functions of circular RNAs
Mısır, S., Wu, N., & Yang, B. B. (2022) · Cell Death and Differentiation · doi:10.1038/s41418-022-00948-7 · Cited by 482 · see citing works
“Disruption of circRNAs has been reported in neurodegenerative diseases, such as Alzheimer’s disease and autism spectrum disorder [61, 62].”
BackgroundCircRNAs: role in human diseases and potential use as biomarkers
Verduci, L., Tarcitano, E., Strano, S., Yarden, Y., & Blandino, G. (2021) · Cell Death and Disease · doi:10.1038/s41419-021-03743-3 · Cited by 377 · see citing works
“Dube et al.(67) generated RNA-seq data from individuals with and without AD to quantify cortical circRNA expression.”
BackgroundReview on circular RNAs and new insights into their roles in cancer
Tang, X., Ren, H., Guo, M., Qian, J., Yang, Y., & Gu, C. (2021) · Computational and Structural Biotechnology Journal · doi:10.1016/j.csbj.2021.01.018 · Cited by 353 · see citing works
“Increasing evidence indicates that circRNAs are closely associated with the pathology of various diseases, including Alzheimer’s disease[21] neurological dysfunction[22] osteoarthritis[23] diabetes[24] cardiac disease[25] and cancer[26].”
BackgroundThe role of N6-methyladenosine (m6A) modification in the regulation of circRNAs
Zhang, L., Hou, C., Chen, C., Guo, Y., Yuan, W., Yin, D., Liu, J., & Sun, Z. (2020) · Molecular Cancer · doi:10.1186/s12943-020-01224-3 · Cited by 334 · see citing works
“It is now generally accepted that circRNA is generated by a process named back-splicing [2], and increasing studies have demonstrated that circRNA plays important roles in the occurrence, development and prognosis of various diseases, including tumorigenesis [3–5], neurodevelopmental processes [6] autoimmune responses…”
BackgroundBiogenesis and Functions of Circular RNAs Come into Focus
Xiao, M., Ai, Y., & Wilusz, J. E. (2020) · Trends in Cell Biology · doi:10.1016/j.tcb.2019.12.004 · Cited by 315 · see citing works
Strianese, O., Rizzo, F. M., Ciccarelli, M., Galasso, G., D’Agostino, Y., Salvati, A., Giudice, C. D., Tesorio, P., & Rusciano, M. R. (2020) · Genes · doi:10.3390/genes11070747 · Cited by 258 · see citing works
The potential of using blood circular RNA as liquid biopsy biomarker for human diseases
Wen, G., Zhou, T., & Gu, W. (2020) · Protein & Cell · doi:10.1007/s13238-020-00799-3 · Cited by 178 · see citing works
Circular RNAs: Expression, localization, and therapeutic potentials
Yang, Q., Li, F., He, A. T., & Yang, B. B. (2021) · Molecular Therapy · doi:10.1016/j.ymthe.2021.01.018 · Cited by 168 · see citing works
isoCirc catalogs full-length circular RNA isoforms in human transcriptomes
Xin, R., Gao, Y. P., Gao, Y., Wang, R., Kadash-Edmondson, K. E., Liu, B., Wang, Y., Lin, L., & Xing, Y. (2021) · Nature Communications · doi:10.1038/s41467-020-20459-8 · Cited by 159 · see citing works
A psychiatric disease-related circular RNA controls synaptic gene expression and cognition
Zimmerman, A. J., Hafez, A. K., Amoah, S. K., Rodriguez, B. A., Dell’Orco, M., Lozano, E., Hartley, B. J., Alural, B., Lalonde, J., Chander, P. N., et al. (2020) · Molecular Psychiatry · doi:10.1038/s41380-020-0653-4 · Cited by 152 · see citing works
“cognitive dysfunction scores [84], we anticipate circHomer1a-mediated control of gene expression to also be of”
BackgroundWei, C., Zhu, M.-X., Lu, N., Liu, J., Yang, Y., Zhang, Y., Shi, Y., Feng, Z., Li, J., Qi, F., et al. (2020) · Molecular Cancer · doi:10.1186/s12943-020-01191-9 · Cited by 152 · see citing works
A Parkinson's disease CircRNAs Resource reveals a link between circSLC8A1 and oxidative stress
Hanan, M., Simchovitz, A., Yayon, N., Vaknine, S., Cohen‐Fultheim, R., Karmon, M., Madrer, N., Rohrlich, T. M., Maman, M., Bennett, E. R., et al. (2020) · EMBO Molecular Medicine · doi:10.15252/emmm.201911942 · Cited by 141 · see citing works
Hanan, M., Simchovitz, A., Yayon, N., Vaknine, S., Cohen‐Fultheim, R., Karmon, M., Madrer, N., Rohrlich, T. M., Maman, M., Bennett, E. R., et al. (2020) · EMBO Molecular Medicine · doi:10.15252/emmm.202013551 · Cited by 127 · see citing works
“Interestingly, several reports have suggested a link between circRNAs and neurodegenerative disorders including Alzheimer’s disease and amyotrophic lateral sclerosis (Lukiw, 2013; Errichelli et al , 2017; Shi et al , 2017; Dube et al , 2019).”
Yang, Z., Huang, C., Wen, X., Liu, W., Huang, X.-X., Li, Y., Zang, J., Weng, Z., Lu, D., Tsang, C. K., et al. (2021) · Molecular Therapy · doi:10.1016/j.ymthe.2021.11.004 · Cited by 118 · see citing works
“These molecules take part in neurovascular functions, such as neurodevelopment(6) and degenerative diseases.(7) Notably, circRNAs protect BBB integrity by targeting miRNAs against ischemic stroke(8) and bacterial meningitis.”
BackgroundCompeting Endogenous RNA Networks as Biomarkers in Neurodegenerative Diseases
Moreno‐García, L., López‐Royo, T., Calvo, A. C., Toivonen, J. M., de la Torre, M., Moreno‐Martínez, L., Molina, N., Aparicio, P., Zaragoza, P., Manzano, R., et al. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21249582 · Cited by 110 · see citing works
“Since CDR1as/ciRS-7 contains over 70 binding sites for miR-7 and has been found to be altered in other NDDs such as AD [46,47] (see above), ciRS-7/miR-7/SNCA axis has been proposed as a possible ceRNET in PD [80–83].”
InfluentialCircular RNA Cwc27 contributes to Alzheimer’s disease pathogenesis by repressing Pur-α activity
Song, C., Zhang, Y., Huang, W., Shi, J., Huang, Q., Jiang, M., Qiu, Y. L., Wang, T., Chen, H., & Wang, H. (2021) · Cell Death and Differentiation · doi:10.1038/s41418-021-00865-1 · Cited by 107 · see citing works
Epigenetic Basis of Lead-Induced Neurological Disorders
Wang, T., Zhang, J., & Xu, Y. (2020) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph17134878 · Cited by 98 · see citing works
“circCORO1C contained two predicted binding sites for miR-105, which is predicted to target APP and SCNA (n = 77) [105] No associations were established.”
BackgroundCircular RNAs in physiology and non-immunological diseases
Chen, L., Huang, C., & Shan, G. (2021) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2021.11.004 · Cited by 98 · see citing works
The function and mechanisms of action of circular RNAs in Urologic Cancer
Zhang, Z.-H., Wang, Y., Zhang, Y., Zheng, S., Feng, T., Tian, X., Abudurexiti, M., Wang, Z.-D., Zhu, W., Su, J., et al. (2023) · Molecular Cancer · doi:10.1186/s12943-023-01766-2 · Cited by 94 · see citing works
Circular RNAs’ cap-independent translation protein and its roles in carcinomas
He, L., Man, C., Xiang, S., Yao, L., Wang, X., & Fan, Y. (2021) · Molecular Cancer · doi:10.1186/s12943-021-01417-4 · Cited by 89 · see citing works
Cheng, Q., Wang, J., Li, M., Fang, J., Ding, H., Meng, J., Zhang, J., Fang, X., Liu, H., Ma, C., et al. (2022) · Redox Biology · doi:10.1016/j.redox.2022.102430 · Cited by 89 · see citing works
Self-citationOu, R., Lu, S., Wang, L., Wang, Y., Lv, M., Li, T., Xu, Y., Lu, J., & Ge, R. (2022) · Frontiers in Oncology · doi:10.3389/fonc.2022.858598 · Cited by 87 · see citing works
“Emerging evidence has demonstrated that dysregulated circRNAs exert a crucial role in human diseases, including cancer (14, 15), cardiovascular disease (16), diabetes (17), and Alzheimer’s disease (18).”
BackgroundLiu, Y., Li, X., Dong, L., Wang, J., Xiao, Q., Yu, X., & Zhu, H. (2020) · Cancer Management and Research · doi:10.2147/cmar.s239326 · Cited by 84 · see citing works
Self-citationExportin 4 depletion leads to nuclear accumulation of a subset of circular RNAs
Chen, L., Wang, Y., Lin, J., Song, Z., Wang, Q., Zhao, W., Wang, Y., Xiu, X., Deng, Y., Li, X., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-33356-z · Cited by 84 · see citing works
NOVA2 regulates neural circRNA biogenesis
Knupp, D., Cooper, D. A., Saito, Y., Darnell, R. B., & Miura, P. (2021) · Nucleic Acids Research · doi:10.1093/nar/gkab523 · Cited by 76 · see citing works
“Some circRNAs have been recently associated with neurological defects in mice (34) and humans (36,75).”
BackgroundCircular RNAs in the human brain are tailored to neuron identity and neuropsychiatric disease
Dong, X., Bai, Y., Liao, Z., Gritsch, D., Liu, X., Wang, T., Borges-Monroy, R., Ehrlich, A., Serrano, G. E., Feany, M. Β., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-40348-0 · Cited by 78 · see citing works
“Previous studies have examined circRNAs mostly in bulk tissues and lacked cellular resolution 5,8 , and standard single-cell sequencing methods have been limited to linear and in many cases, polyadenylated RNAs.”
InfluentialCircular RNA Encoded Amyloid Beta peptides—A Novel Putative Player in Alzheimer’s Disease
Mo, D., Li, X., Raabe, C. A., Rozhdestvensky, T. S., Skryabin, B. V., & Brosius, J. (2020) · Cells · doi:10.3390/cells9102196 · Cited by 74 · see citing works
“report that 10 circRNAs have strong pathological associations with AD [55].”
BackgroundMa, N., Pan, J., Ye, X., Yu, B., Zhang, W., & Wan, J. (2019) · Molecular Therapy — Nucleic Acids · doi:10.1016/j.omtn.2019.10.030 · Cited by 73 · see citing works
“Molecular Thera for humanADcase status, indicating that themechanism of circRNA in AD development needs to be further elucidated.(57)”
BackgroundCSF proteomics identifies early changes in autosomal dominant Alzheimer’s disease
Shen, Y., Timsina, J., Heo, G., Beric, A., Ali, M., Wang, C., Yang, C., Wang, Y., Western, D., Liu, M., et al. (2024) · Cell · doi:10.1016/j.cell.2024.08.049 · Cited by 75 · see citing works
Self-citationRNA Dynamics in Alzheimer’s Disease
Rybak‐Wolf, A., & Plass, M. (2021) · Molecules · doi:10.3390/molecules26175113 · Cited by 70 · see citing works
Liquid Biopsy in Neurological Diseases
Malhotra, S., Miras, M. C. M., Pappolla, A., Montalbán, X., & Comabella, M. (2023) · Cells · doi:10.3390/cells12141911 · Cited by 69 · see citing works
“Additionally, a separate study reported increased cirHomer1 and hsa_circ_0131235 expressions associated with AD pathology [47,48].”
BackgroundRavanidis, S., Bougea, A., Karampatsi, D., Papagiannakis, N., Maniati, M., Stefanis, L., & Doxakis, E. (2021) · Movement Disorders · doi:10.1002/mds.28467 · Cited by 63 · see citing works
Emerging functions of circular RNA in aging
Kim, E., Kim, Y. K., & Lee, S. (2021) · Trends in Genetics · doi:10.1016/j.tig.2021.04.014 · Cited by 68 · see citing works
Liu, H., Jin, M., Ji, M., Zhang, W., Liu, A., & Wang, T. (2022) · Aging · doi:10.18632/aging.203989 · Cited by 71 · see citing works
Diverse lncRNA mechanisms in brain development and disease
Ang, C. E., Trevino, A. E., & Chang, H. Y. (2020) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2020.05.006 · Cited by 64 · see citing works
Brain high-throughput multi-omics data reveal molecular heterogeneity in Alzheimer’s disease
Eteleeb, A. M., Novotny, B. C., Tarraga, C. S., Sohn, C., Dhungel, E., Brase, L., Nallapu, A., Buss, J., Farias, F., Bergmann, K., et al. (2024) · PLOS Biology · doi:10.1371/journal.pbio.3002607 · Cited by 64 · see citing works
Self-citationLiu, L., Chen, X., Chen, Y., & Zhang, K. (2020) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2020.601965 · Cited by 62 · see citing works
“Recently, the significant associations between circRNA expression in the parietal cortex and AD diagnosis, clinical dementia severity, and neuropathological severity have been well-explained (Umber et al., 2019).”
BackgroundAli, M., Timsina, J., Western, D., Liu, M., Beric, A., Budde, J., Do, A., Heo, G., Wang, L., Gentsch, J., et al. (2025) · Neuron · doi:10.1016/j.neuron.2025.02.014 · Cited by 61 · see citing works
Self-citationCircular RNAs: The Brain Transcriptome Comes Full Circle
Gokoolparsadh, A., Loy, C. T., Halliday, G. M., & Voineagu, I. (2020) · Trends in Neurosciences · doi:10.1016/j.tins.2020.07.007 · Cited by 60 · see citing works
RNA dysregulation in neurodegenerative diseases
Li, Y., & Sun, S. (2025) · The EMBO Journal · doi:10.1038/s44318-024-00352-6 · Cited by 62 · see citing works
“For example, circHOMER1, the levels of which decrease with increasing dementia severity, possesses fi ve predicted binding sites for miR-651, whose downstream targets include the AD-related genes PSEN1 and PSEN2, suggesting a potential sponging mechanism of this circRNA (Dube et al, 2019).”
Recent insights into the roles of circular RNAs in human brain development and neurologic diseases
Najafi, S., Zarch, S. M. A., Majidpoor, J., Pordel, S., Aghamiri, S., Rasul, M. F., Asemani, Y., Vakili, O., Mohammadi, V., Movahedpour, A., et al. (2022) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2022.11.166 · Cited by 55 · see citing works
Assessing circular RNAs in Alzheimer's disease and frontotemporal lobar degeneration
Cervera‐Carles, L., Dols‐Icardo, O., Molina‐Porcel, L., Alcolea, D. A., González, A. C., Muñoz, L., & Clarimón, J. (2020) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2020.03.017 · Cited by 53 · see citing works
Lo, I., Hill, J., Vilhjálmsson, B. J., & Kjems, J. (2020) · RNA Biology · doi:10.1080/15476286.2020.1783487 · Cited by 53 · see citing works
“Recently, research demonstrated the correlation between circRNA expression and the pathological features of AD(Dube et al., 2019).”
BackgroundHafez, A. K., Zimmerman, A. J., Papageorgiou, G., Chandrasekaran, J., Amoah, S. K., Lin, R., Lozano, E., Pierotti, C. E., Dell’Orco, M., Hartley, B. J., et al. (2020) · Cell Reports · doi:10.1016/j.celrep.2021.110282 · Cited by 52 · see citing works
Identification of circRNAs linked to Alzheimer's disease and related dementias
Puri, S., Hu, J., Sun, Z., Lin, M., Stein, T. D., Farrer, L. A., Wolozin, B. L., & Zhang, X. (2023) · Alzheimer s & Dementia · doi:10.1002/alz.12960 · Cited by 54 · see citing works
Wang, X., Xie, J., Tan, L., Lu, Y., Shen, N., Li, J., Hu, H., Li, H., Li, X., & Cheng, L. (2023) · Translational Neurodegeneration · doi:10.1186/s40035-023-00386-6 · Cited by 54 · see citing works
“They are abundantly enriched in neural tissues, specifically derived from synapse-related genes, and their expression is regulated by synaptic plasticity [5, 6].”
BackgroundInfluentialExploring the regulatory roles of circular RNAs in Alzheimer’s disease
Zhang, Y., Zhao, Y., Liu, Y., Wang, M., Yu, W., & Zhang, L. (2020) · Translational Neurodegeneration · doi:10.1186/s40035-020-00216-z · Cited by 47 · see citing works
Li, C., Ren, J., Zhang, M., Wang, H., Fang, Y., Wu, J., & Tang, Y. (2022) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-022-04536-3 · Cited by 50 · see citing works
“For example, circRNA expression significantly correlates with the neuropathological and clinical severity of AD [172].”
BackgroundEpigenetics: Recent Advances and Its Role in the Treatment of Alzheimer's Disease
Xiao, X., Liu, X., & Jiao, B. (2020) · Frontiers in Neurology · doi:10.3389/fneur.2020.538301 · Cited by 50 · see citing works
Inhibition of A1 Astrocytes and Activation of A2 Astrocytes for the Treatment of Spinal Cord Injury
Wang, J., Cheng, C., Liu, Z., Lin, Y., Yang, L., Zhang, Z., Sun, X., Zhou, M., Jing, P., & Zhong, Z. (2022) · Neurochemical Research · doi:10.1007/s11064-022-03820-9 · Cited by 48 · see citing works
“A growing number of studies in recent years have discovered that circRNAs play an important role in central nervous system disorders such as stroke [101], Parkinson’s disease [102] and Alzheimer’s disease [103, 104].”
BackgroundSelf-citationPerezGrovas‐Saltijeral, A., Rajkumar, A. P., & Knight, H. M. (2023) · Molecular Neurobiology · doi:10.1007/s12035-022-03195-6 · Cited by 45 · see citing works
Functional roles of circular RNAs in Alzheimer’s disease
Huang, J.-L., Su, M., & Wu, D. (2020) · Ageing Research Reviews · doi:10.1016/j.arr.2020.101058 · Cited by 45 · see citing works
Neuronal VCP loss of function recapitulates FTLD-TDP pathology
Wani, A., Zhu, J., Ulrich, J. D., Eteleeb, A. M., Sauerbeck, A. D., Reitz, S. J., Arhzaouy, K., Ikenaga, C., Yuede, C. M., Pittman, S. K., et al. (2021) · Cell Reports · doi:10.1016/j.celrep.2021.109399 · Cited by 44 · see citing works
Self-citationCircular RNAs: Emblematic Players of Neurogenesis and Neurodegeneration
D’Anca, M., Buccellato, F. R., Fenoglio, C., & Galimberti, D. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23084134 · Cited by 44 · see citing works
“circDOCK1 Axonal outgrowth, spine morphogenesis, neuroinflammation Brain, plasma Yes Dedicator of cytokinesis 1 [62,65]”
BackgroundShao, L., Jiang, G.-T., Yang, X., Zeng, M., Cheng, J., Kong, S., Dong, X., Chen, T.-X., Han, S. H., Yin, J., et al. (2021) · The FASEB Journal · doi:10.1096/fj.202001737rr · Cited by 42 · see citing works
Circular RNAs : emerging players in brain aging and neurodegenerative diseases
Wu, D., Zhao, Y., Yan, Q., Liu, L., Wei, Y., & Huang, J. (2022) · The Journal of Pathology · doi:10.1002/path.6021 · Cited by 42 · see citing works
“Meta-analysis showed that circHOMER1 was correlated with the clinical severity of AD patients [25].”
BackgroundResultWelden, J. R., Margvelani, G., Maquera, K. A. A., Gudlavalleti, B., Sardón, S. C. M., Campos, A. R., Robil, N., Lee, D. C., Hernandez, A. G., Wang, W., et al. (2022) · Nucleic Acids Research · doi:10.1093/nar/gkac1129 · Cited by 42 · see citing works
“When taken together, the expression of 10 of these circRNAs predict clinical dementia in human post-mortem samples (61).”
BackgroundDell’Orco, M., Oliver, R. J., & Perrone‐Bizzozero, N. I. (2020) · Frontiers in Genetics · doi:10.3389/fgene.2020.00790 · Cited by 42 · see citing works
The Emerging Role of Circular RNAs in Alzheimer’s Disease and Parkinson’s Disease
Zhang, M., & Bian, Z. (2021) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2021.691512 · Cited by 40 · see citing works
“In addition, circHOMER1 was also significantly related to Braak score and AD status (Dube et al., 2019).”
BackgroundUrdánoz‐Casado, A., de Gordoa, J. S., Robles, M., Acha, B., Roldán, M., Zelaya, M. V., Blanco‐Luquin, I., & Mendióroz, M. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22179205 · Cited by 42 · see citing works
“Our result is concordant with a previous study where a RNAseq experiment was performed in human parietal lobe tissue to identify and quantify circRNAs related to AD [24].”
BackgroundMethodResultInfluentialDoxakis, E. (2022) · npj Parkinson s Disease · doi:10.1038/s41531-021-00265-9 · Cited by 43 · see citing works
Guo, L.-X., Wang, L., You, Z., Yu, C.-Q., Hu, M.-L. M., Zhao, B.-W., & Li, Y. (2024) · Briefings in Bioinformatics · doi:10.1093/bib/bbae020 · Cited by 41 · see citing works
“For instance, Wu et al . investigated the potential miRNA-binding sites in circRNAs associated with Alzheimer’s disease (AD), specifically focusing on miRNAs that are implicated in targeting AD-related genes [9].”
BackgroundCircular RNAs: Promising biomarkers for cancer diagnosis and prognosis
Wei, G., Zhu, J., Hu, H., & Liu, J. (2020) · Gene · doi:10.1016/j.gene.2020.145365 · Cited by 41 · see citing works
RNA-sequencing of peripheral blood circular RNAs in Parkinson disease
Kong, F., Lv, Z., Wang, L., Zhang, K., Cai, Y., Ding, Q., Sun, Z., Zhen, H., Jiao, F., Ma, Q., et al. (2021) · Medicine · doi:10.1097/md.0000000000025888 · Cited by 41 · see citing works
“The expression of 2 circRNAs, hsa_circ_0001439 and hsa_circ_0014606, also were changed in Alzheimer disease.([38]) The expression of hsa_circ_0001439 was up-regulated in Brodmann Area 10 (BM10) of patients who suffered from Alzheimer disease.”
BackgroundUncovering the impact of noncoding variants in neurodegenerative brain diseases
Frydas, A., Wauters, E., van der Zee, J., & Broeckhoven, C. V. (2021) · Trends in Genetics · doi:10.1016/j.tig.2021.08.010 · Cited by 42 · see citing works
“Cyrano enables accumulation of circRNA Cdr1as, a circRNA that dampens neuronal function in mouse brain [118] and is differentially expressed in AD brain [108].”
BackgroundHatzimanolis, O., Sykes, A. M., & Cristino, A. S. (2025) · Molecular Psychiatry · doi:10.1038/s41380-025-02925-1 · Cited by 42 · see citing works
“A meta-analysis has provided an atlas of circRNA expression changes in cortical regions of AD patients, revealing signi fi cant correlations with clinical and neuropathological traits of AD [278].”
Liang, S., Dou, S., Li, W., & Huang, Y. (2020) · Aging · doi:10.18632/aging.103683 · Cited by 40 · see citing works
Ikeda, Y., Morikawa, S., Nakashima, M., Yoshikawa, S., Taniguchi, K., Sawamura, H., Suga, N., Tsuji, A., & Matsuda, S. (2023) · Non-Coding RNA · doi:10.3390/ncrna9020023 · Cited by 39 · see citing works
“Furthermore, circRNAs have been recognized as potential biomarkers in other diseases including amyotrophic lateral sclerosis (ALS), diabetes, and glioblastoma [43].”
BackgroundInfluentialMetabolomic and lipidomic signatures in autosomal dominant and late‐onset Alzheimer's disease brains
Novotny, B. C., Fernández, M. V., Wang, C., Budde, J., Bergmann, K., Eteleeb, A. M., Bradley, J. L., Webster, C., Ebl, C., Norton, J. B., et al. (2022) · Alzheimer s & Dementia · doi:10.1002/alz.12800 · Cited by 37 · see citing works
Self-citationCircular RNAs in human diseases
Wang, Y., Zhang, J., Yang, Y. S. H., Liu, Z., Sun, S., Li, R. F., Zhu, H., Tian, L., Zheng, J., Li, J., et al. (2024) · MedComm · doi:10.1002/mco2.699 · Cited by 40 · see citing works
de Bartolomeis, A., Barone, A., Buonaguro, E. F., Tomasetti, C., Vellucci, L., & Iasevoli, F. (2022) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2022.104596 · Cited by 37 · see citing works
Wei, S.-H., Liu, M., Hu, J., & Zhang, C. (2022) · Analytical Chemistry · doi:10.1021/acs.analchem.2c01901 · Cited by 36 · see citing works
Fernández, M. V., Liu, M., Beric, A., Johnson, M., Cetin, A., Patel, M. R., Budde, J., Kohlfeld, P., Bergmann, K., Lowery, J., et al. (2024) · Scientific Data · doi:10.1038/s41597-024-03485-9 · Cited by 41 · see citing works
“GHTO researchers demonstrated for the first time that brain circRNAs are causally associated with AD 12 .”
BackgroundSelf-citationBiomarkers in neurodegenerative diseases: a broad overview
Sathish, S., & Ayyavoo, V. (2024) · Exploration of Neuroprotective Therapy · doi:10.37349/ent.2024.00075 · Cited by 38 · see citing works
Li, S., Hu, W., Deng, F., Chen, S., Zhu, P., Wang, M., Chen, X., Wang, Y., Hu, X., Zhao, B., et al. (2021) · DNA and Cell Biology · doi:10.1089/dna.2020.5662 · Cited by 35 · see citing works
“Indeed, multiple previous studies have explored the utility of circRNAs as novel biomarkers of human disease (Huang et al. , 2016; Shang et al. , 2016; Dube et al. , 2019; Wang et al. , 2019).”
Suster, I., & Feng, Y. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22136765 · Cited by 37 · see citing works
Nguyen, L. D., Chau, R. K., & Krichevsky, A. M. (2021) · Genes · doi:10.3390/genes12122005 · Cited by 34 · see citing works
New RNA-Based Breakthroughs in Alzheimer’s Disease Diagnosis and Therapeutics
Riscado, M., Baptista, B., & de Sousa, F. P. (2021) · Pharmaceutics · doi:10.3390/pharmaceutics13091397 · Cited by 34 · see citing works
“Dube and colleagues have shown that the expression of circRNAs changes before the appearance of significant onset symptoms of AD, demonstrating that circRNAs levels can be correlated with neuropathological and clinical evaluation of AD severity [75].”
BackgroundDysregulation of RNA modification systems in clinical populations with neurocognitive disorders
Knight, H. M., Öz, M. D., & PerezGrovas‐Saltijeral, A. (2023) · Neural Regeneration Research · doi:10.4103/1673-5374.385858 · Cited by 33 · see citing works
“As circular RNAs can regulate mRNA through binding to RNA-binding proteins and have been shown to be abnormally expressed in brain diseases (Dube et al., 2019), these observations highlight the potential for a more complex transcriptional regulatory system involving NSUN6 underlying AD and TBI…”
BackgroundLiu, X.-X., Xiong, W., Ye, M., Lu, T.-S., Yuan, K., Chang, S., Han, Y., Wang, Y.-X., Lu, L., & Bao, Y.-P. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01669-0 · Cited by 30 · see citing works
Circular RNAs in Alzheimer’s Disease: A New Perspective of Diagnostic and Therapeutic Targets
Vakili, O., Asili, P., Babaei, Z., Mirahmad, M., Keshavarzmotamed, A., Asemi, Z., & Mafi, A. (2022) · CNS & Neurological Disorders - Drug Targets · doi:10.2174/1871527321666220829164211 · Cited by 32 · see citing works
Regulatory mechanism of circular RNAs in neurodegenerative diseases
Xiao, F., He, Z., Wang, S., Li, J., Fan, X., Yan, T., Yang, M., & Yang, D. (2023) · CNS Neuroscience & Therapeutics · doi:10.1111/cns.14499 · Cited by 29 · see citing works
Non-Coding RNAs as Sensors of Oxidative Stress in Neurodegenerative Diseases
Gámez‐Valero, A., Guisado-Corcoll, A., Herrero‐Lorenzo, M., Solaguren‐Beascoa, M., & Martı́, E. (2020) · Antioxidants · doi:10.3390/antiox9111095 · Cited by 31 · see citing works
“Specifically, ciRS-7 is downregulated in the grey matter of AD patients’ cortex [160,161].”
BackgroundCircular RNAs in the Central Nervous System
Li, M., Wang, W., & Jin, Z. (2021) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2021.629593 · Cited by 31 · see citing works
“levels are significantly correlated with both neuropathological and clinical measures of AD severity (Dube et al., 2019).”
BackgroundCircular RNAs: new biomarkers of chemoresistance in cancer
Wang, J., Zhang, Y., Liu, L., Yang, T., & Song, J. (2021) · Cancer Biology and Medicine · doi:10.20892/j.issn.2095-3941.2020.0312 · Cited by 31 · see citing works
Self-citationCompeting endogenous RNA network mediated by circ_3205 in SARS-CoV-2 infected cells
Barbagallo, D., Palermo, C. I., Barbagallo, C., Battaglia, R., Caponnetto, A., Spina, V., Ragusa, M., Pietro, C. D., Scalia, G., & Purrello, M. (2022) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-021-04119-8 · Cited by 31 · see citing works
“CircRNAs have been found aberrantly expressed in many cancers and degenerative diseases [19, 20] and are associated with several biological processes, both in physiological and pathological conditions [21–24].”
BackgroundChen, H., Eteleeb, A. M., Wang, C., Fernández, M. V., Budde, J., Bergmann, K., Norton, J. B., Wang, F., Ebl, C., Morris, J. C., et al. (2022) · Acta Neuropathologica Communications · doi:10.1186/s40478-022-01328-5 · Cited by 29 · see citing works
“A previous study [20], demonstrated that expression changes of circRNAs in pre-symptomatic AD, sporadic AD, and ADAD are different and not always related to severity of the disease.”
InfluentialSelf-citationSystematic review and meta-analysis on microRNAs in amyotrophic lateral sclerosis
Liu, H., Lan, S., Shi, X., Fan, F.-C., Liu, Q., Cong, L., & Cheng, Y. (2023) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2023.01.005 · Cited by 31 · see citing works
Vascular endothelial‐cadherin as a marker of endothelial injury in preclinical Alzheimer disease
Tarawneh, R. M., Kasper, R. S., Sanford, J., Phuah, C., Hassenstab, J. J., & Cruchaga, C. (2022) · Annals of Clinical and Translational Neurology · doi:10.1002/acn3.51685 · Cited by 29 · see citing works
“Post-mortem brain sections were available from a subset of participants (n = 96) with preclinical AD (n = 83)(52,53) and healthy controls (n = 13) and evaluated by singlenucleus RNA (snRNA) sequence analyses for differential VEC brain expression levels.(54,55) Functional pathway analyses for VEC in human brains were p…”
MethodSelf-citationConserved gene signatures shared among MAPT mutations reveal defects in calcium signaling
Minaya, M., Mahali, S. K., Iyer, A. K., Eteleeb, A. M., Martinez, R. J., Huang, G., Budde, J., Temple, S., Nana, A. L., Seeley, W. W., et al. (2023) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2023.1051494 · Cited by 26 · see citing works
“To determine whether gene expression changes in iPSC-neuron models reflect a more general impact on neurodegenerative pathways, we examined gene expression profiles isolated from tissue of FTLD-TDP caused by rare mutations theGRN,C9ORF72 expansions, or from sporadic cases (Knight ADRC)(Li et al., 2018; Dube et al., 20…”
BackgroundSelf-citationLi, Y., Wang, F., Teng, P., Ku, L., Chen, L., Feng, Y., & Yao, B. (2022) · Genome biology · doi:10.1186/s13059-022-02621-1 · Cited by 29 · see citing works
“Mounting evidence has also demonstrated that dysregulation of circRNAs is involved in human neurological disorders, including Alzheimer’s disease, Parkinson’s disease, and Schizophrenia [17, 18, 75].”
BackgroundSelf-citationPierouli, K., Papakonstantinou, E., Papageorgiou, L., Diakou, I., Mitsis, Τ., Dragoumani, K., Spandidos, D. A., Bacopoulou, F., Chrousos, G. P., Goulielmos, G. N., et al. (2022) · International Journal of Molecular Medicine · doi:10.3892/ijmm.2022.5208 · Cited by 29 · see citing works
“miR‐520c (42) circHOMER1 (63,84) piR‐34393 (92) NAT‐Rad18 (104,105)”
Expression and function of circular RNAs in the mammalian brain
Xu, K., Zhang, Y., & Li, J. (2021) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-021-03780-3 · Cited by 27 · see citing works
Decoding the complexity of circular RNAs in cardiovascular disease
Rai, A. K., Lee, B., Hebbard, C., Uchida, S., & Garikipati, V. N. S. (2021) · Pharmacological Research · doi:10.1016/j.phrs.2021.105766 · Cited by 28 · see citing works
CircSNHG5 Sponges Mir-495-3p and Modulates CITED2 to Protect Cartilage Endplate From Degradation
Zhang, J., Hu, S., Ding, R., Yuan, J., Jia, J., Wu, T., & Cheng, X. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.668715 · Cited by 27 · see citing works
Circular RNAs in atherosclerosis
Huang, X., Zhao, Y., Zhou, H., & Li, Y. (2022) · Clinica Chimica Acta · doi:10.1016/j.cca.2022.03.016 · Cited by 27 · see citing works
- Authors
- Dube, U., Del-Aguila, J. L., Li, Z., Budde, J. P., Jiang, S., Hsu, S., Ibanez, L., Fernandez, M. V., Farias, F., Norton, J., Gentsch, J., Wang, F., the Dominantly Inherited Alzheimer Network (DIAN), Allegri, R., Amtashar, F., Benzinger, T., Berman, S., Bodge, C., Brandon, S., Brooks, W., Buck, J., Buckles, V., Chea, S., Chrem, P., Chui, H., Cinco, J., Clifford, J., D’Mello, M., Donahue, T., Douglas, J., Edigo, N., Erekin-Taner, N., Fagan, A., Farlow, M., Farrar, A., Feldman, H., Flynn, G., Fox, N., Franklin, E., Fujii, H., Gant, C., Gardener, S., Ghetti, B., Goate, A., Goldman, J., Gordon, B., Gray, J., Gurney, J., Hassenstab, J., Hirohara, M., Holtzman, D., Hornbeck, R., DiBari, S. H., Ikeuchi, T., Ikonomovic, S., Jerome, G., Jucker, M., Kasuga, K., Kawarabayashi, T., Klunk, W., Koeppe, R., Kuder-Buletta, E., Laske, C., Levin, J., Marcus, D., Martins, R., Mason, N. S., Maue-Dreyfus, D., McDade, E., Montoya, L., Mori, H., Nagamatsu, A., Neimeyer, K., Noble, J., Norton, J., Perrin, R., Raichle, M., Ringman, J., Roh, J. H., Schofield, P., Shimada, H., Shiroto, T., Shoji, M., Sigurdson, W., Sohrabi, H., Sparks, P., Suzuki, K., Swisher, L., Taddei, K., Wang, J., Wang, P., Weiner, M., Wolfsberger, M., Xiong, C., Xu, X., Salloway, S., Masters, C. L., Lee, J.-H., Graff-Radford, N. R., Chhatwal, J. P., Bateman, R. J., Morris, J. C., Karch, C. M., Harari, O., & Cruchaga, C.
- Affiliations
- Washington University in St. Louis (US)
- Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia (AR)
- University of Pittsburgh (US)
- Indiana University Bloomington (US)
- Mayo Clinic (US)
- University of Southern California (US)
- Edith Cowan University (AU)
- Columbia University (US)
- Hirosaki University (JP)
- German Center for Neurodegenerative Diseases (DE)
- University of Michigan (US)
- Osaka City University (JP)
- The University of Tokyo (JP)
- Asan Medical Center (KR)
- Brigham and Women's Hospital (US)
- University of California, San Francisco (US)
- The University of Melbourne (AU)
- University of Ulsan (KR)
- Harvard University (US)
- Corresponding author
- Cruchaga, Carlos
- ORCID
- Dube, Umber
- Li, Zeran
- Budde, John P
- Jiang, Shan
- Hsu, Simon
- Wang, Fengxian
- Allegri, Ricardo
- Benzinger, Tammie
- Berman, Sarah
- Brooks, William
- D’Mello, Mirelle
- Fagan, Anne
- Feldman, Howard
- Fox, Nick
- Franklin, Erin
- Fujii, Hisako
- Gardener, Samantha
- Ghetti, Bernardino
- Goate, Alison
- Goldman, Jill
- Gordon, Brian
- Gurney, Jenny
- Hassenstab, Jason
- Holtzman, David
- Hornbeck, Russ
- Ikeuchi, Takeshi
- Jucker, Mathias
- Kasuga, Kensaku
- Kawarabayashi, Takeshi
- Klunk, William
- Laske, Christoph
- Levin, Johannes
- Martins, Ralph
- McDade, Eric
- Mori, Hiroshi
- Noble, James
- Perrin, Richard
- Ringman, John
- Roh, Jee Hoon
- Schofield, Peter
- Shoji, Mikio
- Sohrabi, Hamid
- Suzuki, Kazushi
- Taddei, Kevin
- Wang, Jen
- Xiong, Chengjie
- Salloway, Stephen
- Masters, Colin L
- Lee, Jae-Hong
- Chhatwal, Jasmeer P
- Bateman, Randall J
- Morris, John C
- Karch, Celeste M
- Harari, Oscar
- Cruchaga, Carlos
- Venue
- Nature Neuroscience
- Published
- 2019-10-07
- Volume
- 22
- Issue
- 11
- Pages
- 1903-1912
- ISSN
- 1097-6256 (ISSN-L)
- 1546-1726
- PMC
- PMC6858549
- OpenAlex
- W2977553419
- Cited by
- 345
- References
- 63
- Citations by year
- 2026: 22 · 2025: 43 · 2024: 45 · 2023: 53 · 2022: 69 · 2021: 60 · 2020: 48 · 2019: 3
- FWCI
- 14.89
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Nature Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Murdoch University Research Portal (submittedVersion)
- UWA Profiles and Research Repository (UWA) (submittedVersion)
- Edith Cowan University Research Online (Edith Cowan University) (submittedVersion)
- UCL Discovery (University College London) (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- DZNE Pub (submittedVersion)
- Funders
- U.S. Department of Health & Human Services | NIH | National Institute on Aging (RF1AG053303, R01AG058501, RF1AG058501)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Circular RNAs in diseases
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- circular RNA, Alzheimer's disease, parietal cortex, autosomal dominant Alzheimer's disease, microRNA binding sites, non-coding RNA, brain transcriptome
- MeSH terms
- RNA, Circular, Alzheimer Disease, Atlases as Topic, Humans, Parietal Lobe, RNA, Messenger, Severity of Illness Index, Case-Control Studies, Sequence Analysis, RNA, Gene Expression Profiling, MicroRNAs
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
