Altered cell and RNA isoform diversity in aging Down syndrome brains
Open accessAbstract
Down syndrome (DS), trisomy of human chromosome 21 (HSA21), is characterized by lifelong cognitive impairments and the development of the neuropathological hallmarks of Alzheimer’s disease (AD). The cellular and molecular modifications responsible for these effects are not understood. Here we performed single-nucleus RNA sequencing (snRNA-seq) employing both short- (Illumina) and long-read (Pacific Biosciences) sequencing technologies on a total of 29 DS and non-DS control prefrontal cortex samples. In DS, the ratio of inhibitory-to-excitatory neurons was significantly increased, which was not observed in previous reports examining sporadic AD. DS microglial transcriptomes displayed AD-related aging and activation signatures in advance of AD neuropathology, with increased microglial expression of C1q complement genes (associated with dendritic pruning) and the HSA21 transcription factor gene RUNX1 . Long-read sequencing detected vast RNA isoform diversity within and among specific cell types, including numerous sequences that differed between DS and control brains. Notably, over 8,000 genes produced RNAs containing intra-exonic junctions, including amyloid precursor protein ( APP ) that had previously been associated with somatic gene recombination. These and related results illuminate large-scale cellular and transcriptomic alterations as features of the aging DS brain.
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In tissue from the prefrontal cortex of adolescents and young adults with Down syndrome (13-32 years), no difference in percentage of interneurons (measured by GAD67 protein expression) was identified, but the proportion of interneurons to total neurons was significantly increased in Down syndrome.
“Again, no difference in percentage of interneurons (measured by GAD67 protein expression) was identified, but the proportion of interneurons to total neurons was significantly increased in DS (Palmer et al., 2021).”
From Neurodevelopment in Down syndrome: Concordance in humans and models (2022) · cites this paper as Palmer et al., 2021
Split into 2 atoms — 1 confirmed, 0 partially supported, 1 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
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Experimental — accuracy not yet measuredThere is substantial evidence of neuropathology from early in life in DS, including defects in neuronal development, increased ratio of inhibitory to excitatory neurons, alterations in neuronal dendritic spine dynamics, activation of microglia, astrocyte reactivity, and elevated production of inflammatory cytokines in the brain.
“There is substantial evidence of neuropathology from early in life in DS,6,9,10,21 including defects in neuronal development, an increased ratio of inhibitory to excitatory neurons, alterations in neuronal dendritic spines dynamics, activation of microglia, astrocyte reactivity, and elevated production of inflammatory cytokines in the brain.22,23,24,25”
From Interferon signaling modulates Down syndrome-associated Alzheimer’s disease pathology in a mouse model (2025) · cites this paper as [24]
Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
Experimental — accuracy not yet measuredRecent studies indicate an increased ratio of inhibitory to excitatory neurons in the cortex and hippocampus in Dp16 mice that is associated with deficits in learning, memory, and motor function.
“recent studies that indicate an increased ratio of inhibitory to excitatory neurons in the cortex and hippocampus in Dp16 mice that is associated with deficits in learning, memory, and motor function.”
From Interferon signaling modulates Down syndrome-associated Alzheimer’s disease pathology in a mouse model (2025) · cites this paper as [24]
The Results section on DS prefrontal cortex reports an increased proportion of inhibitory neurons in human Down syndrome brains and notes a similar imbalance in the Ts65Dn mouse model. It does not establish that the ratio is increased in the cortex and hippocampus of Dp16 mice or associate that ratio with learning, memory, and motor deficits. The passage mentioning Dp16 instead concerns dendritic spine density. (LLM, conf=0.87)
Experimental — accuracy not yet measuredThe fraction of neurons that expressed ADARB2 was significantly increased in the samples from individuals with Down syndrome, while the fraction of neurons that expressed LHX6 was significantly decreased.
“Interestingly, the fraction of neurons that expressed ADARB2 was significantly increased in the samples from individuals with DS, while the fraction of neurons that expressed LHX6 was significantly decreased.”
From Neurodevelopment in Down syndrome: Concordance in humans and models (2022) · cites this paper as Palmer et al., 2021
The Results section on neuronal subtype alterations reports that ADARB2-expressing neurons were overrepresented in Down syndrome brains (Fig. 1G; P < 0.01). It says LHX6-expressing neurons were present at similar proportions to controls, not significantly decreased. (LLM, conf=0.90)
Experimental — accuracy not yet measuredSingle nucleus RNA-seq identified six clusters of inhibitory neurons that expressed ADARB2, indicating they arose from the CGE, and four clusters that expressed LHX6, indicating they arose from the MGE.
“They identified six clusters of inhibitory neurons that expressed ADARB2, indicating they arose from the CGE, and four clusters that expressed LHX6, indicating they arose from the MGE.”
From Neurodevelopment in Down syndrome: Concordance in humans and models (2022) · cites this paper as Palmer et al., 2021
The Results section on neuronal subtype alterations links ADARB2-expressing inhibitory neurons to the CGE and LHX6-expressing neurons to the MGE, and reports that this distinction is observed in humans. It identifies the groups as In1–In4 and In6–In8, however, and does not substantiate the claimed counts of six ADARB2 clusters and four LHX6 clusters. (LLM, conf=0.88)
Experimental — accuracy not yet measured
Elevated expression of APP was found in many cell types in the frontal cortex, consistent with a previous report.
“Consistent with a previous report, we found elevated expression of APP in many cell types in the frontal cortex (Fig. 2m, n) [51].”
From Apolipoprotein E abundance is elevated in the brains of individuals with Down syndrome–Alzheimer’s disease (2025) · cites this paper as [51]
The Results section on HSA21 genes reports that APP expression was altered in both excitatory and inhibitory neurons in Down syndrome prefrontal cortex. The section on differential isoform expression says APP RNA is expressed across several cell types, but it does not establish elevated APP expression in many cell types relative to controls. The cited report therefore supports a narrower finding than the one attributed to it. (LLM, conf=0.82)
Experimental — accuracy not yet measuredAPP transcription is elevated in many cell types in the brains of people with DSAD, including cell types in which APOE expression is also raised.
“Consistent with previous reports [49, 51], we observe that APP transcription is elevated in many cell types in the brains of people with DSAD, including cell types in which we find APOE expression is also raised.”
From Apolipoprotein E abundance is elevated in the brains of individuals with Down syndrome–Alzheimer’s disease (2025) · cites this paper as [51]
The Results section on HSA21 genes reports altered APP expression in both excitatory and inhibitory neurons, and the Discussion identifies APP among genes showing dosage effects in specific cell types. The Results section on RNA isoforms says many cell types express APP, but does not establish that its transcription is elevated across many cell types in DSAD or in the same cells with raised APOE. The citing authors describe the APOE overlap as their own finding. (LLM, conf=0.81)
Experimental — accuracy not yet measuredEmerging long-read sequencing approaches enable profiling cellular transcriptomes at isoform resolution.
“Emerging long-read sequencing approaches enable us to profile cellular transcriptomes at isoform resolution,8,31,32,33 thus providing new opportunities to model the relationships between isoforms using co-expression network analysis.”
From hdWGCNA identifies co-expression networks in high-dimensional transcriptomics data (2023) · cites this paper as [32]
With the addition of an older cohort (39-65 years), an increase in the fraction of ADARB2 expressing interneurons was identified, but no difference in LHX6 interneurons was found.
“Again, an increase in the fraction of ADARB2 expressing interneurons was identified, but no difference in LHX6 interneurons was found.”
From Neurodevelopment in Down syndrome: Concordance in humans and models (2022) · cites this paper as Palmer et al., 2021
Recent transcriptomic studies have demonstrated changes in the inhibitory-to-excitatory neuronal ratio and microglial cell states in the brain of people with DS.
“Recent transcriptomic studies have begun to address this by systematically interrogating how the extra copy of Hsa21 alters transcript expression within the brain of people with DS, demonstrating changes in the inhibitory-to-excitatory neuronal ratio, and microglial cell states [49, 51].”
From Apolipoprotein E abundance is elevated in the brains of individuals with Down syndrome–Alzheimer’s disease (2025) · cites this paper as [51]
DSAD has changes to neuroimmune biology compared with AD in the general population.
“changes to neuroimmune biology [46, 51, 67]”
From Apolipoprotein E abundance is elevated in the brains of individuals with Down syndrome–Alzheimer’s disease (2025) · cites this paper as [51]
The raised levels of APOE are consistent with a growing body of data indicating that the neuroimmune system differs in people with DS.
“The raised levels of APOE are consistent with a growing body of data indicating that the neuroimmune system differs in people with DS [15, 34, 46, 51, 53, 66, 67].”
From Apolipoprotein E abundance is elevated in the brains of individuals with Down syndrome–Alzheimer’s disease (2025) · cites this paper as [51]
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Cites
Gene Ontology: tool for the unification of biology
Ashburner, M., Ball, C. A., Blake, J. A., Botstein, D., Butler, H., Cherry, J. M., Davis, A. P., Dolinski, K., Dwight, S. S., Eppig, J. T., et al. (2000) · Nature Genetics · doi:10.1038/75556 · Cited by 43,206 · see citing works
Comprehensive Integration of Single-Cell Data
Stuart, T., Butler, A., Hoffman, P., Hafemeister, C., Papalexi, E., Mauck, W. M., Hao, Y., Stoeckius, M., Smibert, P., & Satija, R. (2019) · Cell · doi:10.1016/j.cell.2019.05.031 · Cited by 15,453 · see citing works
A Unique Microglia Type Associated with Restricting Development of Alzheimer’s Disease
Keren-Shaul, H., Spinrad, A., Weiner, A., Matcovitch-Natan, O., Dvir-Szternfeld, R., Ulland, T. K., David, E., Baruch, K., Lara-Astaiso, D., Toth, B., et al. (2017) · Cell · doi:10.1016/j.cell.2017.05.018 · Cited by 5,493 · see citing works
Reversed graph embedding resolves complex single-cell trajectories
Qiu, X., Mao, Q., Tang, Y., Wang, L., Chawla, R., Pliner, H. A., & Trapnell, C. (2017) · Nature Methods · doi:10.1038/nmeth.4402 · Cited by 5,070 · see citing works
The Gene Ontology Resource: 20 years and still GOing strong
The Gene Ontology Consortium (2019) · Nucleic Acids Research · doi:10.1093/nar/gky1055 · Cited by 4,747 · see citing works
Harold, D., Abraham, R., Hollingworth, P., Sims, R., Gerrish, A., Hamshere, M. L., Pahwa, J. S., Moskvina, V., Dowzell, K., Williams, A., et al. (2009) · Nature Genetics · doi:10.1038/ng.440 · Cited by 3,326 · see citing works
The Classical Complement Cascade Mediates CNS Synapse Elimination
Stevens, B., Allen, N. J., Vazquez, L. E., Howell, G. R., Christopherson, K. S., Nouri, N., Micheva, K. D., Mehalow, A. K., Huberman, A. D., Stafford, B., et al. (2007) · Cell · doi:10.1016/j.cell.2007.10.036 · Cited by 3,313 · see citing works
Mi, H., Muruganujan, A., Ebert, D., Huang, X., & Thomas, P. D. (2018) · Nucleic Acids Research · doi:10.1093/nar/gky1038 · Cited by 2,950 · see citing works
Single-cell transcriptomic analysis of Alzheimer’s disease
Mathys, H., Davila-Velderrain, J., Peng, Z., Gao, F., Mohammadi, S., Young, J. Z., Menon, M., He, L., Abdurrob, F., Jiang, X., et al. (2019) · Nature · doi:10.1038/s41586-019-1195-2 · Cited by 2,568 · see citing works
Genome-wide association study identifies variants at CLU and CR1 associated with Alzheimer's disease
the European Alzheimer's Disease Initiative Investigators, Lambert, J.-C., Heath, S., Even, G., Campion, D., Sleegers, K., Hiltunen, M., Combarros, O., Zelenika, D., Bullido, M. J., et al. (2009) · Nature Genetics · doi:10.1038/ng.439 · Cited by 2,234 · see citing works
Amyloid Beta: Structure, Biology and Structure-Based Therapeutic Development
Chen, G.-F., Xu, T.-H., Yan, Y., Zhou, Y.-R., Jiang, Y., Melcher, K., & Xu, H. E. (2017) · Acta Pharmacologica Sinica · doi:10.1038/aps.2017.28 · Cited by 1,965 · see citing works
Parker, S. E., Mai, C. T., Canfield, M. A., Rickard, R., Wang, Y., Meyer, R. E., Anderson, P., Mason, C. A., Collins, J. S., Kirby, R. S., et al. (2010) · Birth Defects Research Part A Clinical and Molecular Teratology · doi:10.1002/bdra.20735 · Cited by 1,887 · see citing works
Mapping Patterns of c- fos Expression in the Central Nervous System After Seizure
Morgan, J. I., Cohén, D., Hempstead, J. L., & Curran, T. (1987) · Science · doi:10.1126/science.3037702 · Cited by 1,778 · see citing works
Conserved cell types with divergent features in human versus mouse cortex
Hodge, R. D., Bakken, T. E., Miller, J. A., Smith, K. A., Barkan, E. R., Graybuck, L. T., Close, J. L., Long, B., Johansen, N., Penn, O., et al. (2019) · Nature · doi:10.1038/s41586-019-1506-7 · Cited by 1,775 · cited 1× · see citing works
“…technologies have opened new avenues to understanding cellular transcriptomics, particularly through the use of single-nucleus RNA sequencing (snRNA-seq), which has been applied to normal (11, 12) and diseased (13–15) human brains, but has not been reported for postnatal or aging DS brains.”
The Prefrontal Cortex—An Update
Fuster, J. M. (2001) · Neuron · doi:10.1016/s0896-6273(01)00285-9 · Cited by 1,760 · see citing works
Shared and distinct transcriptomic cell types across neocortical areas
Tasic, B., Yao, Z., Graybuck, L. T., Smith, K. A., Nguyen, T. N., Bertagnolli, D., Goldy, J., Garren, E., Economo, M. N., Viswanathan, S., et al. (2018) · Nature · doi:10.1038/s41586-018-0654-5 · Cited by 1,746 · see citing works
Microglia in neurodegeneration
Hickman, S., Izzy, S., Sen, P., Morsett, L., & El Khoury, J. (2018) · Nature Neuroscience · doi:10.1038/s41593-018-0242-x · Cited by 1,710 · see citing works
Spatial and temporal heterogeneity of mouse and human microglia at single-cell resolution
Masuda, T., Sankowski, R., Staszewski, O., Böttcher, C., Amann, L., Sagar, Scheiwe, C., Nessler, S., Kunz, P., van Loo, G., et al. (2019) · Nature · doi:10.1038/s41586-019-0924-x · Cited by 1,310 · see citing works
Occurrence of neuropathological changes and dementia of Alzheimer’s disease in Down’s syndrome
Wisniewski, K. E., Wisniewski, H. M., & Wen, G. Y. (1985) · Annals of Neurology · doi:10.1002/ana.410170310 · Cited by 1,159 · see citing works
Scotti, M. M., & Swanson, M. S. (2015) · Nature Reviews Genetics · doi:10.1038/nrg.2015.3 · Cited by 1,130 · see citing works
A benchmark of batch-effect correction methods for single-cell RNA sequencing data
Tran, H. T. N., Ang, K. S., Chevrier, M., Zhang, X., Lee, N. Y. S., Goh, M., & Chen, J. (2020) · Genome Biology · doi:10.1186/s13059-019-1850-9 · Cited by 1,113 · see citing works
Integrative single-cell analysis of transcriptional and epigenetic states in the human adult brain
Lake, B. B., Chen, S., Sos, B. C., Fan, J., Kaeser, G. E., Yung, Y. C., Duong, T. E., Gao, D., Chun, J., Kharchenko, P. V., et al. (2018) · Nature Biotechnology · doi:10.1038/nbt.4038 · Cited by 983 · see citing works
Self-citationNegative feedback control of neuronal activity by microglia
Badimon, A., Strasburger, H. J., Ayata, P., Chen, X., Nair, A., Ikegami, A., Hwang, P., Chan, A. T., Graves, S. M., Uweru, J. O., et al. (2020) · Nature · doi:10.1038/s41586-020-2777-8 · Cited by 979 · see citing works
Single-cell genomics identifies cell type–specific molecular changes in autism
Velmeshev, D., Schirmer, L., Jung, D., Haeussler, M., Perez, Y., Mayer, S., Bhaduri, A., Goyal, N., Rowitch, D. H., & Kriegstein, A. R. (2019) · Science · doi:10.1126/science.aav8130 · Cited by 927 · see citing works
Antisense oligonucleotides: the next frontier for treatment of neurological disorders
Rinaldi, C., & Wood, M. J. A. (2018) · Nature Reviews Neurology · doi:10.1038/nrneurol.2017.148 · Cited by 788 · see citing works
Temporal Tracking of Microglia Activation in Neurodegeneration at Single-Cell Resolution
Mathys, H., Adaikkan, C., Gao, F., Young, J. Z., Manet, E., Hemberg, M., De Jager, P. L., Ransohoff, R. M., Regev, A., & Tsai, L.-H. (2017) · Cell Reports · doi:10.1016/j.celrep.2017.09.039 · Cited by 740 · see citing works
Neuronal vulnerability and multilineage diversity in multiple sclerosis
Schirmer, L., Velmeshev, D., Holmqvist, S., Kaufmann, M., Werneburg, S., Jung, D., Vistnes, S., Stockley, J. H., Young, A., Steindel, M., et al. (2019) · Nature · doi:10.1038/s41586-019-1404-z · Cited by 638 · see citing works
Microglia mediate forgetting via complement-dependent synaptic elimination
Wang, C., Yue, H., Hu, Z., Shen, Y., Ma, J., Li, J., Wang, X.-D., Wang, L., Sun, B., Shi, P., et al. (2020) · Science · doi:10.1126/science.aaz2288 · Cited by 629 · see citing works
Multiple roles of eph receptors and ephrins in neural development
Wilkinson, D. G. (2001) · Nature reviews. Neuroscience · doi:10.1038/35058515 · Cited by 614 · see citing works
A genetic cause of Alzheimer disease: mechanistic insights from Down syndrome
Wiseman, F. K., Al-Janabi, T., Hardy, J., Karmiloff-Smith, A., Nizetic, D., Tybulewicz, V. L. J., Fisher, E. M. C., & Strydom, A. (2015) · Nature Reviews Neuroscience · doi:10.1038/nrn3983 · Cited by 562 · see citing works
Miyoshi, G., Hjerling-Leffler, J., Karayannis, T., Sousa, V. H., Butt, S. J. B., Battiste, J., Johnson, J. E., Machold, R. P., & Fishell, G. (2010) · The Journal of Neuroscience · doi:10.1523/jneurosci.4515-09.2010 · Cited by 559 · see citing works
Raj, B., & Blencowe, B. J. (2015) · Neuron · doi:10.1016/j.neuron.2015.05.004 · Cited by 475 · see citing works
Kleschevnikov, A. M., Belichenko, P. V., Villar, A. J., Epstein, C. J., Malenka, R. C., & Mobley, W. C. (2004) · The Journal of Neuroscience · doi:10.1523/jneurosci.1766-04.2004 · Cited by 459 · see citing works
Tardáguila, M., de la Fuente, L., Martí, C., Pereira, C., Pardo-Palacios, F. J., del Risco, H., Ferrell, M., Mellado-López, M., Macchietto, M. G., Verheggen, K., et al. (2018) · Genome Research · doi:10.1101/gr.222976.117 · Cited by 441 · see citing works
Single-cell isoform RNA sequencing characterizes isoforms in thousands of cerebellar cells
Gupta, I., Collier, P. G., Haase, B., Mahfouz, A., Joglekar, A., Floyd, T., Koopmans, F., Barres, B., Smit, A. B., Sloan, S. A., et al. (2018) · Nature Biotechnology · doi:10.1038/nbt.4259 · Cited by 343 · see citing works
Non-epithelial stem cells and cortical interneuron production in the human ganglionic eminences
Hansen, D. V., Lui, J. H., Flandin, P., Yoshikawa, K., Rubenstein, J. L., Alvarez-Buylla, A., & Kriegstein, A. R. (2013) · Nature Neuroscience · doi:10.1038/nn.3541 · Cited by 328 · see citing works
Gene therapy for neurological disorders: progress and prospects
Deverman, B. E., Ravina, B. M., Bankiewicz, K. S., Paul, S. M., & Sah, D. W. Y. (2018) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2018.110 · Cited by 306 · see citing works
Down syndrome: the brain in trisomic mode
Dierssen, M. (2012) · Nature reviews. Neuroscience · doi:10.1038/nrn3314 · Cited by 273 · see citing works
Erratum: Gene therapy for neurological disorders: progress and prospects
Deverman, B. E., Ravina, B. M., Bankiewicz, K. S., Paul, S. M., & Sah, D. W. Y. (2018) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2018.158 · Cited by 248 · see citing works
Gene expression profiling in the adult Down syndrome brain
Lockstone, H. E., Harris, L. W., Swatton, J. E., Wayland, M. T., Holland, A. J., & Bahn, S. (2007) · Genomics · doi:10.1016/j.ygeno.2007.08.005 · Cited by 240 · see citing works
Olmos-Serrano, J. L., Kang, H. J., Tyler, W. A., Silbereis, J. C., Cheng, F., Zhu, Y., Pletikos, M., Jankovic-Rapan, L., Cramer, N. P., Galdzicki, Z., et al. (2016) · Neuron · doi:10.1016/j.neuron.2016.01.042 · Cited by 239 · cited 3× · see citing works
“, Rescuing over-activated microglia restores cognitive performance in juvenile animals of the Dp(16) mouse model of Down syndrome.”
Signaling from Axon Guidance ReceptorsPreprint
Bashaw, G. J., & Klein, R. (2010) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a001941 · Cited by 238 · see citing works
A spatially resolved brain region- and cell type-specific isoform atlas of the postnatal mouse brain
Joglekar, A., Prjibelski, A., Mahfouz, A., Collier, P., Lin, S., Schlusche, A. K., Marrocco, J., Williams, S. R., Haase, B., Hayes, A., et al. (2021) · Nature Communications · doi:10.1038/s41467-020-20343-5 · Cited by 229 · see citing works
Interaction of Reelin with Amyloid Precursor Protein Promotes Neurite Outgrowth
Hoe, H.-S., Lee, K. J., Carney, R. S. E., Lee, J., Markova, A., Lee, J.-Y., Howell, B. W., Hyman, B. T., Pak, D. T. S., Bu, G., et al. (2009) · Journal of Neuroscience · doi:10.1523/jneurosci.4872-08.2009 · Cited by 219 · see citing works
Li, Z., Yu, T., Morishima, M., Pao, A., LaDuca, J., Conroy, J., Nowak, N., Matsui, S.-I., Shiraishi, I., & Yu, Y. E. (2007) · Human Molecular Genetics · doi:10.1093/hmg/ddm086 · Cited by 218 · see citing works
Somatic APP gene recombination in Alzheimer’s disease and normal neurons
Lee, M.-H., Siddoway, B., Kaeser, G. E., Segota, I., Rivera, R., Romanow, W. J., Liu, C. S., Park, C., Kennedy, G., Long, T., et al. (2018) · Nature · doi:10.1038/s41586-018-0718-6 · Cited by 210 · see citing works
Self-citationTrisomy 21 and early brain development
Haydar, T. F., & Reeves, R. H. (2012) · Trends in Neurosciences · doi:10.1016/j.tins.2011.11.001 · Cited by 200 · see citing works
Alternative Splicing in Neurogenesis and Brain Development
Su, C.-H., Dhananjaya, D., & Tarn, W. (2018) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2018.00012 · Cited by 192 · see citing works
Increased synaptic depression in the Ts65Dn mouse, a model for mental retardation in Down syndrome
Siarey, R. J., Carlson, E. J., Epstein, C. J., Balbo, A., Rapoport, S. I., & Galdzicki, Z. (1999) · Neuropharmacology · doi:10.1016/s0028-3908(99)00083-0 · Cited by 184 · see citing works
Bach1: Function, Regulation, and Involvement in Disease
Zhang, X., Guo, J., Wei, X., Niu, C., Jia, M., Li, Q., & Meng, D. (2018) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2018/1347969 · Cited by 179 · see citing works
A splicing isoform of GPR56 mediates microglial synaptic refinement via phosphatidylserine binding
Li, T., Chiou, B., Gilman, C. K., Luo, R., Koshi, T., Yu, D., Oak, H. C., Giera, S., Johnson‐Venkatesh, E., Muthukumar, A. K., et al. (2020) · The EMBO Journal · doi:10.15252/embj.2019104136 · Cited by 177 · see citing works
A technology-agnostic long-read analysis pipeline for transcriptome discovery and quantificationPreprint
Wyman, D., Balderrama-Gutierrez, G., Reese, F., Jiang, S., Rahmanian, S., Forner, S., Matheos, D. P., Zeng, W., Williams, B. A., Trout, D. E., et al. (2019) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/672931 · Cited by 163 · see citing works
A Chromosome 21 Critical Region Does Not Cause Specific Down Syndrome Phenotypes
Olson, L. E., Richtsmeier, J., Leszl, J. M., & Reeves, R. H. (2004) · Science · doi:10.1126/science.1098992 · Cited by 153 · see citing works
Kougioumtzidou, E., Shimizu, T., Hamilton, N. B., Tohyama, K., Sprengel, R., Monyer, H., Attwell, D., & Richardson, W. D. (2017) · eLife · doi:10.7554/elife.28080 · Cited by 151 · see citing works
Down syndrome: searching for the genetic culprits
Lana-Elola, E., Watson-Scales, S., Fisher, E., & Tybulewicz, V. (2011) · Disease Models & Mechanisms · doi:10.1242/dmm.008078 · Cited by 149 · see citing works
The GABAergic Hypothesis for Cognitive Disabilities in Down Syndrome
Contestabile, A., Magara, S., & Cancedda, L. (2017) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2017.00054 · Cited by 141 · see citing works
Gene dosage effects: nonlinearities, genetic interactions, and dosage compensation
Veitia, R. A., Bottani, S., & Birchler, J. A. (2013) · Trends in Genetics · doi:10.1016/j.tig.2013.04.004 · Cited by 140 · see citing works
Pinto, B., Morelli, G., Rastogi, M., Savardi, A., Fumagalli, A., Petretto, A., Bartolucci, M., Varea, E., Catelani, T., Contestabile, A., et al. (2020) · Neuron · doi:10.1016/j.neuron.2020.09.010 · Cited by 135 · see citing works
de Silva, H. A. R., Jen, A., Wickenden, C., Jen, L., Wilkinson, S. L., & Patel, A. J. (1997) · Molecular Brain Research · doi:10.1016/s0169-328x(97)00045-4 · Cited by 131 · see citing works
In vivo modeling of human neuron dynamics and Down syndrome
Real, R., Peter, M., Trabalza, A., Khan, S., Smith, M. A., Dopp, J., Barnes, S. J., Momoh, A., Strano, A., Volpi, E., et al. (2018) · Science · doi:10.1126/science.aau1810 · Cited by 120 · see citing works
Seizure frequency and characteristics in children with Down syndrome
Goldberg‐Stern, H., Strawsburg, R. H., Patterson, B. J., Hickey, F. J., Bare, M. A., Gadoth, N., & deGrauw, T. J. (2001) · Brain and Development · doi:10.1016/s0387-7604(01)00239-x · Cited by 120 · see citing works
Gribble, S. M., Wiseman, F. K., Clayton, S., Prigmore, E., Langley, E., Yang, F., Maguire, S., Fu, B., Rajan, D., Sheppard, O., et al. (2013) · PLoS ONE · doi:10.1371/journal.pone.0060482 · Cited by 102 · see citing works
Godfrey, M., & Lee, N. (2018) · Journal of Neurodevelopmental Disorders · doi:10.1186/s11689-017-9220-y · Cited by 91 · see citing works
Logan, T. T., Villapol, S., & Symes, A. J. (2013) · PLoS ONE · doi:10.1371/journal.pone.0059250 · Cited by 77 · see citing works
Malko, P., Mortadza, S. A. S., McWilliam, J., & Jiang, L. (2019) · Frontiers in Pharmacology · doi:10.3389/fphar.2019.00239 · Cited by 76 · see citing works
Sheng, L., Leshchyns’ka, I., & Sytnyk, V. (2015) · Journal of Neuroscience · doi:10.1523/jneurosci.1714-14.2015 · Cited by 70 · see citing works
de la Fuente, L., Arzalluz-Luque, Á., Tardáguila, M., del Risco, H., Martí, C., Tarazona, S., Salguero, P., Scott, R., Lerma-Aguilera, A., Alastrue‐Agudo, A., et al. (2020) · Genome biology · doi:10.1186/s13059-020-02028-w · Cited by 66 · see citing works
Microglia recapitulate a hematopoietic master regulator network in the aging human frontal cortex
Wehrspaun, C. C., Haerty, W., & Ponting, C. P. (2015) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2015.04.008 · Cited by 64 · see citing works
Patzke, C., Max, K. E. A., Behlke, J., Schreiber, J., Schmidt, H., Dorner, A. A., Kröger, S., Henning, M., Otto, A., Heinemann, U., et al. (2010) · Journal of Neuroscience · doi:10.1523/jneurosci.5725-09.2010 · Cited by 61 · see citing works
Haas, M. A., Bell, D., Slender, A., Lana-Elola, E., Watson-Scales, S., Fisher, E. M. C., Tybulewicz, V. L. J., & Guillemot, F. (2013) · PLoS ONE · doi:10.1371/journal.pone.0078561 · Cited by 48 · see citing works
Single cell transcriptome in aneuploidies reveals mechanisms of gene dosage imbalance
Stamoulis, G., Garieri, M., Makrythanasis, P., Letourneau, A., Guipponi, M., Panousis, N. I., Béna, F., Falconnet, E., Ribaux, P., Borel, C., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-12273-8 · Cited by 40 · see citing works
Tardáguila, M., de la Fuente, L., Martí, C., Pereira, C., Pardo-Palacios, F. J., del Risco, H., Ferrell, M., Mellado-López, M., Macchietto, M. G., Verheggen, K., et al. (2018) · Genome Research · doi:10.1101/gr.239137.118 · Cited by 35 · see citing works
Regulation of APC development, immune response, and autoimmunity by Bach1/HO-1 pathway in mice
So, A. Y., Garcia-Flores, Y., Minisandram, A., Martin, A., Taganov, K. D., Boldin, M., & Baltimore, D. (2012) · Blood · doi:10.1182/blood-2012-04-426247 · Cited by 31 · see citing works
Simmons, A. B., Bloomsburg, S., Sukeena, J. M., Miller, C. J., Ortega-Burgos, Y., Borghuis, B. G., & Fuerst, P. G. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1713548114 · Cited by 30 · see citing works
Spektor, R., Yang, J. W., Lee, S. Y., & Soloway, P. D. (2019) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/561191 · Cited by 10 · see citing works
Neuronal Cell-Intrinsic Defects in Mouse Models of Down Syndrome
Chiotto, A. M. A., Migliorero, M., Pallavicini, G., Bianchi, F. T., Gai, M., Di Cunto, F., & Berto, G. E. (2019) · Frontiers in Neuroscience · doi:10.3389/fnins.2019.01081 · Cited by 9 · see citing works
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hdWGCNA identifies co-expression networks in high-dimensional transcriptomics data
Morabito, S., Reese, F., Rahimzadeh, N., Miyoshi, E., & Swarup, V. (2023) · Cell Reports Methods · doi:10.1016/j.crmeth.2023.100498 · Cited by 773 · see citing works
Pardo-Palacios, F. J., Arzalluz-Luque, Á., Kondratova, L., Salguero, P., Mestre‐Tomás, J., Amorín, R., Estevan-Morió, E., Liu, T., Nanni, A. V., McIntyre, L. M., et al. (2024) · Nature Methods · doi:10.1038/s41592-024-02229-2 · Cited by 208 · see citing works
Genomics in the long-read sequencing era
van Dijk, E., Naquin, D., Gorrichon, K., Jaszczyszyn, Y., Ouazahrou, R., Thermes, C., & Hernandez, C. (2023) · Trends in Genetics · doi:10.1016/j.tig.2023.04.006 · Cited by 134 · see citing works
Miyoshi, E., Morabito, S., Henningfield, C. M., Das, S., Rahimzadeh, N., Shabestari, S. K., Michael, N., Emerson, N., Reese, F., Shi, Z., et al. (2024) · Nature Genetics · doi:10.1038/s41588-024-01961-x · Cited by 115 · see citing works
Applications of long-read sequencing to Mendelian genetics
Mastrorosa, F. K., Miller, D. E., & Eichler, E. E. (2023) · Genome Medicine · doi:10.1186/s13073-023-01194-3 · Cited by 91 · see citing works
Developmental isoform diversity in the human neocortex informs neuropsychiatric risk mechanisms
Patowary, A., Zhang, P., Jops, C. T., Vuong, C. K., Ge, X., Hou, K., Kim, M., Gong, N. N., Margolis, M. P., Vo, D., et al. (2024) · Science · doi:10.1126/science.adh7688 · Cited by 87 · see citing works
Self-citationIGF1 deficiency integrates stunted growth and neurodegeneration in Down syndrome
Araya, P., Kinning, K. T., Coughlan, C., Smith, K. P., Granrath, R. E., Enriquez-Estrada, B. A., Worek, K., Sullivan, K. D., Rachubinski, A. L., Wolter-Warmerdam, K., et al. (2022) · Cell Reports · doi:10.1016/j.celrep.2022.111883 · Cited by 50 · see citing works
Neurodevelopment in Down syndrome: Concordance in humans and models
Klein, J. A., & Haydar, T. F. (2022) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2022.941855 · Cited by 47 · see citing works
“Again, no difference in percentage of interneurons (measured by GAD67 protein expression) was identified, but the proportion of interneurons to total neurons was significantly increased in DS (Palmer et al., 2021).”
BackgroundAdvances in single-cell long-read sequencing technologies
Gupta, P., O’Neill, H., Wolvetang, E. J., Chatterjee, A., & Gupta, I. (2024) · NAR Genomics and Bioinformatics · doi:10.1093/nargab/lqae047 · Cited by 49 · see citing works
The Two Sides of Siponimod: Evidence for Brain and Immune Mechanisms in Multiple Sclerosis
COHAN, S. L., Benedict, R. H. B., Cree, B., DeLuca, J., Hua, L. H., & Chun, J. J. M. (2022) · CNS Drugs · doi:10.1007/s40263-022-00927-z · Cited by 44 · see citing works
Self-citationHuman brain small extracellular vesicles contain selectively packaged, full-length mRNA
Ransom, L., Liu, C. S., Dunsmore, E., Palmer, C. R., Nicodemus, J., Ziomek, D., Williams, N., & Chun, J. J. M. (2024) · Cell Reports · doi:10.1016/j.celrep.2024.114061 · Cited by 33 · see citing works
Self-citationQuantifying transcriptome diversity: a review
Jones, E. F., Haldar, A., Oza, V. H., & Lasseigne, B. N. (2023) · Briefings in Functional Genomics · doi:10.1093/bfgp/elad019 · Cited by 27 · see citing works
Su, J., Krock, E., Barde, S. S., Delaney, A., Ribeiro, J., Kato, J., Agalave, N. M., Wigerblad, G., Matteo, R., Sabbadini, R. A., et al. (2022) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2022.01.003 · Cited by 27 · see citing works
Self-citationRastogi, M., Bartolucci, M., Nanni, M., Aloisio, M., Vozzi, D., Petretto, A., Contestabile, A., & Cancedda, L. (2024) · Neuron · doi:10.1016/j.neuron.2024.05.002 · Cited by 26 · see citing works
Astroglial and microglial pathology in Down syndrome: Focus on Alzheimer's disease
Garcı́a, O., & Aguilar, L. F. (2022) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2022.987212 · Cited by 25 · see citing works
Asynchronous excitatory neuron development in an isogenic cortical spheroid model of Down syndrome
Li, Z., Klein, J. A., Rampam, S., Kurzion, R., Campbell, N. B., Patel, Y., Haydar, T. F., & Zeldich, E. (2022) · Frontiers in Neuroscience · doi:10.3389/fnins.2022.932384 · Cited by 24 · see citing works
Rodent Modeling of Alzheimer's Disease in Down Syndrome: In vivo and ex vivo Approaches
Farrell, C., Mumford, P., & Wiseman, F. K. (2022) · Frontiers in Neuroscience · doi:10.3389/fnins.2022.909669 · Cited by 22 · see citing works
Rescue of deficits by Brwd1 copy number restoration in the Ts65Dn mouse model of Down syndrome
Fulton, S. L., Wenderski, W., Lepack, A. E., Eagle, A. L., Fanutza, T., Bastle, R. M., Ramakrishnan, A., Hays, E. C., Neal, A., Bendl, J. M., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-34200-0 · Cited by 21 · see citing works
de Lagrán, M. M., Elizalde‐Torrent, A., Paredes, R., Clotet, B., & Dierssen, M. (2022) · Journal of Cellular and Molecular Medicine · doi:10.1111/jcmm.17411 · Cited by 19 · see citing works
Single-cell omics sequencing technologies: the long-read generation
Wen, L., & Tang, F. (2025) · Trends in Genetics · doi:10.1016/j.tig.2025.07.012 · Cited by 17 · see citing works
Cell models for Down syndrome-Alzheimer’s disease research
Wu, Y., West, N. R., Bhattacharyya, A., & Wiseman, F. K. (2022) · Neuronal Signaling · doi:10.1042/ns20210054 · Cited by 17 · see citing works
Wu, Y., Mumford, P., Noy, S., Cleverley, K., Mrzyglod, A., Luo, D., van Dalen, F., Verdoes, M., Fisher, E. M. C., & Wiseman, F. K. (2023) · Acta Neuropathologica Communications · doi:10.1186/s40478-023-01632-8 · Cited by 16 · see citing works
Brandebura, A. N., Paumier, A., Asbell, Q. N., Tao, T., Micael, M. K. B., Sanchez, S., & Allen, N. J. (2025) · Cell Reports · doi:10.1016/j.celrep.2025.116300 · Cited by 17 · see citing works
Vuong, C. K., Weber, A., Seong, P., Matoba, N., Chen, Y.-J., Peyer, J., Younesi, S., Salinda, A., Gomez, D., Rivas, G., et al. (2026) · Science · doi:10.1126/science.aea1259 · Cited by 14 · see citing works
Watson, L. A., & Meharena, H. S. (2023) · Frontiers in Genetics · doi:10.3389/fgene.2023.1198129 · Cited by 13 · see citing works
Molecular and cellular processes disrupted in the early postnatal Down syndrome prefrontal cortex
Risgaard, R. D., Hanthanan Arachchilage, K., Knaack, S. A., Hosseini, M., Chen, R. J., Kumarage, P., Schmidt, D. K., Huang, X., Sheng, J., Wang, C. J., et al. (2026) · Science · doi:10.1126/science.aea1549 · Cited by 12 · see citing works
Qiu, J.-J., Liu, Y.-N., Wei, H., Zeng, F., & Yan, J.-B. (2023) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2023.1137123 · Cited by 12 · see citing works
Neocortical neuronal production and maturation defects in the TcMAC21 mouse model of Down syndrome
Kurabayashi, N., Fujii, K., Otobe, Y., Hiroki, S., Hiratsuka, M., Yoshitane, H., Kazuki, Y., & Takao, K. (2023) · iScience · doi:10.1016/j.isci.2023.108379 · Cited by 13 · see citing works
Shaking up the silence: consequences of HMGN1 antagonizing PRC2 in the Down syndrome brain
Farley, S. J., Grishok, A., & Zeldich, E. (2022) · Epigenetics & Chromatin · doi:10.1186/s13072-022-00471-6 · Cited by 13 · see citing works
Arendt-Tranholm, A., Mwirigi, J. M., & Price, T. J. (2024) · Pain · doi:10.1097/j.pain.0000000000003255 · Cited by 10 · see citing works
Ortega-Gascó, A., Parcerisas, A., Hino, K., Herranz‐Pérez, V., Ulloa, F., Elias-Tersa, A., Bosch, M., García‐Verdugo, J. M., Simó, S., Pujadas, L., et al. (2023) · Cerebral Cortex · doi:10.1093/cercor/bhad340 · Cited by 10 · see citing works
Farrell, C., Buhidma, Y., Mumford, P., Heywood, W. E., Hällqvist, J., Flores-Aguilar, L., Andrews, E. J., Rahimzadah, N., Taso, O. S., Doran, E., et al. (2025) · Acta Neuropathologica · doi:10.1007/s00401-025-02889-0 · Cited by 9 · see citing works
“The raised levels of APOE are consistent with a growing body of data indicating that the neuroimmune system differs in people with DS [15, 34, 46, 51, 53, 66, 67].”
InfluentialRusu, B., Kukreja, B., Wu, T., Dan, S. J., Feng, M.-Y., & Kalish, B. (2023) · eNeuro · doi:10.1523/eneuro.0147-23.2023 · Cited by 2 · see citing works
Chow, T. W., Raupp, M. D., Reynolds, M. W., Li, S., Kaeser, G. E., & Chun, J. J. M. (2024) · Pharmaceuticals · doi:10.3390/ph17040408 · Cited by 8 · see citing works
Self-citationTranscriptional Regulation of Microglial Metabolic and Activation States by P2RY12
Lopez‐Ortiz, A. O., Doceti, M., Thomas, J., Duffy, A., Coburn, M., Okojie, A. K., Lee, A., Sou, E. A., Gaultier, A., & Eyo, U. B. (2025) · Glia · doi:10.1002/glia.70078 · Cited by 11 · see citing works
Zhou, Z., Zhi, C., Chen, D., Cai, Z., & Jiang, X. (2023) · Genes & Genomics · doi:10.1007/s13258-023-01433-2 · Cited by 9 · see citing works
Islam, R., Jackson, B., Naomi, M. T., Schatz, B., Tan, N., Murdock, M. H., Park, D. S., Rodrígues-Amorím, D., Jiang, X., Pineda, S. S., et al. (2025) · PLoS ONE · doi:10.1371/journal.pone.0317428 · Cited by 8 · see citing works
Fernández‐Blanco, Á., Sierra, C., Tejido, C., & Dierssen, M. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25063289 · Cited by 6 · see citing works
RNA Isoform Diversity in Human Neurodegenerative Diseases
Liu, C. S., Park, C. Y., Ngo, T., Saikumar, J., Palmer, C. R., Shahnaee, A., Romanow, W. J., & Chun, J. J. M. (2024) · eNeuro · doi:10.1523/eneuro.0296-24.2024 · Cited by 8 · see citing works
Self-citationLiu, H., Huang, S., Wang, W., Wang, H., Huang, W., Zhai, Z., Wang, D., Fan, Y., Sun, J., Li, D., et al. (2022) · Cell Death and Disease · doi:10.1038/s41419-022-05481-6 · Cited by 8 · see citing works
Cell type characterization of spatiotemporal gene co-expression modules in Down syndrome brain
Seol, S., Kwon, J., & Kang, H. J. (2022) · iScience · doi:10.1016/j.isci.2022.105884 · Cited by 8 · see citing works
Araya, P., Niemeyer, B., Schade, K., Dunn, L. N., Waugh, K., Busquet, N., Brindley, C., Brown, C., Winkler, C., Lyford, H. R., et al. (2025) · iScience · doi:10.1016/j.isci.2025.113130 · Cited by 7 · see citing works
“24,40,44,87 88–90 Another study revealed decrease neurogenesis in the subgranular zone of the hippocampus DG in 5xFAD mice, 91 which plays an important role in cognitive dysfunction.”
Alldred, M. J., Ibrahim, K. W., Pidikiti, H., Chiosis, G., Mufson, E. J., Stutzmann, G. E., & Ginsberg, S. D. (2024) · Acta Neuropathologica Communications · doi:10.1186/s40478-024-01891-z · Cited by 7 · see citing works
Alldred, M. J., Pidikiti, H., Ibrahim, K. W., Lee, S. H., Heguy, A., Hoffman, G. E., Roussos, P., Wısnıewskı, T., Węgiel, J., Stutzmann, G. E., et al. (2024) · Acta Neuropathologica · doi:10.1007/s00401-024-02768-0 · Cited by 7 · see citing works
Detection of APP gene recombinant in human blood plasma
Mitsunaga, S., Fujito, N. T., Nakaoka, H., Imazeki, R., Nagata, E., & Inoue, I. (2023) · Scientific Reports · doi:10.1038/s41598-023-48993-7 · Cited by 7 · see citing works
Green, N. F. O., Sutton, G. J., Pérez‐Burillo, J., Wang, J., Bagot, S., Danon, H. G., Walsh, K., Gokoolparsadh, A., Miles, S. A., Yang, G., et al. (2025) · Nature Neuroscience · doi:10.1038/s41593-025-02154-3 · Cited by 6 · see citing works
Single-cell atlas of the developing Down syndrome brain cortex
Lattke, M., Tan, W. L., Sukumaran, S. K., Utami, K. H., Sintes, M., Sakthivel, S., Tan, J., Lim, A. T. J., Bansal, V. A., Rekopoulou, K., et al. (2026) · Nature Medicine · doi:10.1038/s41591-026-04211-1 · Cited by 8 · see citing works
González-Molina, L. A., Dekker, A. D., Deyn, P. P. D., Dolga, A. M., & Rots, M. G. (2024) · Elsevier eBooks · doi:10.1016/b978-0-443-18516-8.00014-4 · Cited by 6 · see citing works
ZBTB21 suppresses CRE-mediated transcription to impair synaptic function in Down syndrome
Qiao, M., Huang, Q. Q., Wang, X., & Han, J. (2024) · Science Advances · doi:10.1126/sciadv.adm7373 · Cited by 5 · see citing works
Upadhya, S., Klein, J. A., Nathanson, A. J., Holton, K. M., & Barrett, L. E. (2025) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2025.02.011 · Cited by 5 · see citing works
The landscape of differential splicing and transcript alternations in severe COVID ‐19 infection
Mukherjee, S. B., Mukherjee, S., Detroja, R., & Frenkel‐Morgenstern, M. (2023) · FEBS Journal · doi:10.1111/febs.16723 · Cited by 5 · see citing works
Triplication of Synaptojanin 1 in Alzheimer’s Disease Pathology in Down Syndrome
Hwang, R., Dang, L. T., Chen, J., Lee, J. H., & Marquer, C. (2022) · Current Alzheimer Research · doi:10.2174/1567205020666221202102832 · Cited by 4 · see citing works
The X-linked intellectual disability gene CUL4B is critical for memory and synaptic function
Jiang, W., Zhang, J., Wang, Μ., Zou, Y., Liu, Q., Song, Y., Sun, G., Gong, Y., Zhang, F., & Jiang, B. (2024) · Acta Neuropathologica Communications · doi:10.1186/s40478-024-01903-y · Cited by 4 · see citing works
TarDis: Achieving robust and structured disentanglement of multiple covariates
İnecik, K., Kara, A., Rose, A., Haniffa, M. A., & Theis, F. J. (2026) · Cell Systems · doi:10.1016/j.cels.2026.101573 · Cited by 4 · see citing works
Alldred, M. J., Pidikiti, H., Ibrahim, K. W., Lee, S. H., Heguy, A., Chiosis, G., Mufson, E. J., Stutzmann, G. E., & Ginsberg, S. D. (2025) · Biomolecules · doi:10.3390/biom15081131 · Cited by 3 · see citing works
mRNA Isoforms and Variants in Health and Disease
Shila, S., Dahiya, V., Hisle, C., Bahadursingh, E., Thiyagarajan, R., Fields, P. E., & Rumi, M. A. K. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26199356 · Cited by 5 · see citing works
Silva, A. L. T. E., de Oliveira, P. H. P., Yokota-Moreno, B. Y., Fausto, J. D. S., Avila, J. P., Nakaya, H. I., Sertie, A. L., & Zampieri, B. L. (2025) · Acta Neuropathologica Communications · doi:10.1186/s40478-025-02090-0 · Cited by 5 · see citing works
Niu, R., Xue, L., Tian, X., Huangfu, L., Chen, L., Zhai, C.-Y., Wang, S., Zhao, Y., Gan, Z., Qin, H.-Y., et al. (2025) · Nature Communications · doi:10.1038/s41467-025-66109-9 · Cited by 3 · see citing works
Self-citationXiong, L., He, R. Q., Du, R., Niu, R., Xue, L., Chen, L., Huangfu, L., Xiao, Q., Li, J., Li, Y., et al. (2025) · MedComm · doi:10.1002/mco2.70114 · Cited by 3 · see citing works
Single-cell sequencing: promises and challenges for human genetics
Sreenivasan, V. K. A., Henck, J., & Spielmann, M. (2022) · Medizinische Genetik · doi:10.1515/medgen-2022-2156 · Cited by 3 · see citing works
Kim, M., Vo, D., Jops, C. T., Wen, C. H., Patowary, A., Bhattacharya, A., Yap, C. X., Zhou, H., & Gandal, M. J. (2022) · medRxiv · doi:10.1101/2022.10.18.22281204 · Cited by 3 · see citing works
Development of Molecular Neuropathology in Down Syndrome across the Lifespan
Bhattacharyya, A., de la Torre-Ubieta, L., Zhu, Y., Head, E., Swarup, V., & Sousa, A. M. M. (2025) · Journal of Neuroscience · doi:10.1523/jneurosci.1365-25.2025 · Cited by 3 · see citing works
Astroglial Activation Is Exacerbated in a Down Syndrome Mouse Model
Zhou, Z., Bi, Y., Zhi, C., Chen, S., Chen, D., Wei, Z. C., & Jiang, X. (2024) · Neuroscience · doi:10.1016/j.neuroscience.2024.04.003 · Cited by 2 · see citing works
Accelerated Tempo of Cortical Neurogenesis in Down SyndromePreprint
Ding, J., Kim, C. N., Steyert, M. R., Yuan, A. T., Shin, D., Ivanov, D., Nowakowski, T. J., & Pollen, A. A. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.09.29.679346 · Cited by 2 · see citing works
Sun, C., Thomas, R. W., Stringer, C. A., Galani, K., Ho, L., Sun, N., Renfro, A., Wright, S. T., Firenze, R. M., Tsai, L., et al. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.04.17.719050 · Cited by 2 · see citing works
isoSeQL: comparing long-read isoforms across multiple datasets
Liu, C. S., & Chun, J. J. M. (2025) · Bioinformatics · doi:10.1093/bioinformatics/btaf680 · Cited by 1 · see citing works
Self-citationShahnaee, A., Liu, C. S., Ngo, T., Palmer, C. R., Ziomek, D., Park, C. S., Tan, V. P., Jimenez, N. A., & Chun, J. J. M. (2026) · Communications Biology · doi:10.1038/s42003-026-09759-9 · Cited by 1 · see citing works
Self-citationUse of anti–amyloid‐β monoclonal antibodies in persons with Down syndrome Alzheimer's disease
Farrell, C., Saini, F., Beidas, M. M., Ryan, N. S., Strydom, A., & Wiseman, F. K. (2026) · Alzheimer s & Dementia · doi:10.1002/alz.71404 · Cited by 1 · see citing works
The Role of Genetic Alterations in the Emergence of Alzheimer's Disease in Down Syndrome: A Review
Robles, C. V., Robles, C. V., Revilla, A. P. A., Suárez‐Valencia, V. D. J., & Salinas-Santander, M. A. (2026) · European Journal of Neuroscience · doi:10.1111/ejn.70623 · Cited by 1 · see citing works
Torkenczy, K. A., Reineke, L. C., Dooling, S. W., Henderson, B. W., Yang, B. A., He, D.-Z., Myers, R. M., Walter, P., Tyanova, S., & Costa-Mattioli, M. (2026) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.2537017123 · Cited by 1 · see citing works
Extraction and Purification of Single Nuclei from Frozen Human Brain Tissue
Palmer, C. R., & Chun, J. J. M. (2022) · Methods in molecular biology · doi:10.1007/978-1-0716-2655-9_2 · Cited by 1 · see citing works
Self-citationAssessment of language abilities and functionality in adults and elders with Down syndrome
Carvalho, C. L., Forlenza, O. V., & Radanovic, M. (2025) · Dementia & Neuropsychologia · doi:10.1590/1980-5764-dn-2024-0224 · Cited by 1 · see citing works
Wu, Y., Mumford, P., Noy, S., Cleverley, K., Mrzyglod, A., Luo, D., van Dalen, F. J., Verdoes, M., Fisher, E., & Wiseman, F. K. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.06.20.545700 · Cited by 1 · see citing works
Mapping the ISR Landscape in Cognitive Disorders via single-cell multi-omicsPreprint
Torkenczy, K. A., Reineke, L. C., Dooling, S. W., Henderson, B., Itzhak, D. N., Yang, B. A., He, D., Myers, R., Walter, P., Tyanova, S., et al. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.02.28.640905 · Cited by 1 · see citing works
Probiotics as Anti-aging Interventions
Singh, B., Mal, G., Kalra, R. S., & Marotta, F. (2024) · Springer eBooks · doi:10.1007/978-3-031-65459-6_12
Somatic Genomic (Genetic) Mosaicism in the Brain
Chun, J. J. M. (2025) · Elsevier eBooks · doi:10.1016/b978-0-323-95702-1.00482-6
Self-citationBartesaghi, R., Chen, X., Johnstone, A. D., Das, U., & Mobley, W. C. (2025) · Springer eBooks · doi:10.1007/978-3-031-89307-0_19
Proteo-transcriptomic reprogramming and resource reallocation define the aging mammalian brainPreprint
Hemandhar-Kumar, N., Kluever, V., Kaufmann, S. V., Bergmann, C., Mousaei, K., Tomas, M., Marrero, M. C., Chopra, A., Hirose, M., Pallàs, M., et al. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.08.14.669896
de Souza, J. S., Sánchez-Sánchez, S. M., Amelinez-Robles, N., Guerra, B. S., Giannocco, G., & Muotri, A. R. (2025) · Cells · doi:10.3390/cells14181407
Wu, Y., Mumford, P., Noy, S., Cleverley, K., Mrzyglod, A., Luo, D., van Dalen, F., Verdoes, M., Fisher, E., & Wiseman, F. K. (2023) · Figshare · doi:10.6084/m9.figshare.23949660
Lattke, M., Tan, W. L., Sukumaran, S. K., Utami, K. H., Sintes, M., Sakthivel, S., Tan, J., Lim, A. T. J., Bansal, V. A., Rekopoulou, K., et al. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2025.12.29.696602
Trisomy 21 Drives ADARB1 Overexpression and Premature RNA Recoding in the Developing Fetal Brain
Breen, M. S., Yang, A., Wang, X., Santos, M. R. D. L., Ran, T. A. O., Weinberger, D. R., Kleinman, J. E., Mihova, K. Y., Stancheva, G. S., Savova, S., et al. (2026) · Nature Communications · doi:10.1038/s41467-026-70217-5
Alldred, M. J., Ibrahim, K. W., Pidikiti, H., Lee, S. H., Heguy, A., Chiosis, G., Mufson, E. J., Stutzmann, G. E., & Ginsberg, S. D. (2026) · The FASEB Journal · doi:10.1096/fj.202504243r
Ma, X., Wang, M., Yang, J., Li, G., Wang, Y., Fang, H., & Zhang, S. (2026) · Neuroinformatics · doi:10.1007/s12021-025-09749-y
Multiomics and proteomic insights into Alzheimer’s disease biology in Down syndrome
Martá-Ariza, M., & Wisniewski, T. R. (2026) · Expert Review of Neurotherapeutics · doi:10.1080/14737175.2026.2695187
Microglial P2ry12 in the Basolateral Amygdala Underlies Neuropathic Pain‐Induced Anxiety
Yang, X.-H., Chen, L., Shi, Q.-X., Liu, H.-M., & Tang, Y.-Y. (2026) · Glia · doi:10.1002/glia.70196
The splicing axis of aging: mechanisms and therapeutic opportunities
Raza, S., Kumari, A., & Cieśla, M. (2026) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2026.09.001
The Role of the Immunoglobulin Superfamily of Cell Adhesion Molecules in Intellectual Disability
Zaman, N., Bui, K., & Sytnyk, V. (2026) · Cells · doi:10.3390/cells15191801
- Authors
- Palmer, C. R., Liu, C. S., Romanow, W. J., Lee, M.-H., & Chun, J.
- Affiliations
- Sanford Burnham Prebys Medical Discovery Institute (US)
- Corresponding author
- Chun, Jerold
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2021-11-18
- Volume
- 118
- Issue
- 47
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC8617492
- OpenAlex
- W3214599091
- Cited by
- 89
- References
- 76
- Citations by year
- 2026: 16 · 2025: 23 · 2024: 17 · 2023: 16 · 2022: 17
- FWCI
- 10.83
- Type
- journal article
- Language
- en
- Update notices
- correction (2022-09-09)
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Funders
- HHS | NIH | National Institute on Aging (R56AG073965, R01AG065541, R01AG071465)
- HHS | NIH | National Institute of General Medical Sciences (T32GM007752)
- Topics
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Down syndrome and intellectual disability research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Single-cell and spatial transcriptomics
- Keywords
- Down syndrome, brain aging, Alzheimer's disease, prefrontal cortex, single-nucleus RNA sequencing, microglia, RUNX1, amyloid precursor protein, long-read sequencing, dendritic pruning
- MeSH terms
- Aging, Alzheimer Disease, Brain, Chromosomes, Human, Pair 21, Down Syndrome, Humans, RNA, Up-Regulation, Gene Expression, Amyloid beta-Protein Precursor, Sequence Analysis, RNA, Microglia, Core Binding Factor Alpha 2 Subunit, RNA Isoforms
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