CD33: increased inclusion of exon 2 implicates the Ig V-set domain in Alzheimer’s disease susceptibility
Open accessAbstract
We previously demonstrated that the Alzheimer's disease (AD) associated risk allele, rs3865444(C), results in a higher surface density of CD33 on monocytes. Here, we find alternative splicing of exon 2 to be the primary mechanism of the genetically driven differential expression of CD33 protein. We report that the risk allele, rs3865444(C), is associated with greater cell surface expression of CD33 in both subjects of European and African-American ancestry and that there is a single haplotype influencing CD33 surface expression. A meta-analysis of the two populations narrowed the number of significant SNPs in high linkage disequilibrium (LD) (r(2) > 0.8) with rs3865444 to just five putative causal variants associated with increased protein expression. Using gene expression data from flow-sorted CD14(+)CD16(-) monocytes from 398 healthy subjects of three populations, we show that the rs3865444(C) risk allele is strongly associated with greater expression of CD33 exon 2 (pMETA = 2.36 × 10(-60)). Western blotting confirms increased protein expression of the full-length CD33 isoform containing exon 2 relative to the rs3865444(C) allele (P < 0.0001). Of the variants in strong LD with rs3865444, rs12459419, which is located in a putative SRSF2 splice site of exon 2, is the most likely candidate to mediate the altered alternative splicing of CD33's Immunoglobulin V-set domain 2 and ultimately influence AD susceptibility.
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The protective CD33 SNP alters CD33 mRNA splicing such that the extracellular sialic acid-binding domain is lost from the final protein.
“The protective SNP alters CD33 mRNA splicing such that the extracellular sialic acid–binding domain is lost from the final protein (Malik et al., 2013, 2015; Raj et al., 2014).”
From Microglia in Alzheimer’s disease (2018) · cites this paper as Raj et al., 2014
Genetic risk can also be mediated through mRNA splicing.
“In addition, it is becoming increasingly clear that genetic risk can also be mediated through mRNA splicing28,29.”
From Genetic analysis of the human microglial transcriptome across brain regions, aging and disease pathologies (2022) · cites this paper as [29]
The CD33 locus in AD influences CD33 splicing, resulting in isoforms with different biological and likely pathological functions.
“For instance, the CD33 locus in AD influences CD33 splicing, resulting in isoforms with different biological and likely pathological functions29.”
From Genetic analysis of the human microglial transcriptome across brain regions, aging and disease pathologies (2022) · cites this paper as [29]
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Browning, S. R., & Browning, B. L. (2007) · The American Journal of Human Genetics · doi:10.1086/521987 · Cited by 3,138 · see citing works
<i>TREM2</i> Variants in Alzheimer's Disease
Guerreiro, R., Wojtas, A., Bras, J., Carrasquillo, M., Rogaeva, E., Majounie, E., Cruchaga, C., Sassi, C., Kauwe, J. S. K., Younkin, S., et al. (2013) · New England Journal of Medicine · doi:10.1056/nejmoa1211851 · Cited by 3,020 · see citing works
LocusZoom: regional visualization of genome-wide association scan results
Pruim, R. J., Welch, R. P., Sanna, S., Teslovich, T. M., Chines, P. S., Gliedt, T. P., Boehnke, M., Abecasis, G. R., & Willer, C. J. (2010) · Bioinformatics · doi:10.1093/bioinformatics/btq419 · Cited by 2,707 · see citing works
Variant of <i>TREM2</i> Associated with the Risk of Alzheimer's Disease
Jonsson, T., Stefansson, H., Steinberg, S., Jonsdottir, I., Jonsson, P. V., Snaedal, J., Bjornsson, S., Huttenlocher, J., Levey, A. I., Lah, J. J., et al. (2013) · New England Journal of Medicine · doi:10.1056/nejmoa1211103 · Cited by 2,558 · see citing works
Siglecs and their roles in the immune system
Crocker, P. R., Paulson, J. C., & Varki, A. P. (2007) · Nature reviews. Immunology · doi:10.1038/nri2056 · Cited by 2,032 · see citing works
Initiative, T. A. D. N., Hollingworth, P., CHARGE consortium, EADI1 consortium, Harold, D., Sims, R., Gerrish, A., Lambert, J.-C., Carrasquillo, M. M., Abraham, R., et al. (2011) · Nature Genetics · doi:10.1038/ng.803 · Cited by 1,997 · see citing works
Naj, A. C., Jun, G., Beecham, G. W., Wang, L.-S., Vardarajan, B. N., Buros, J., Gallins, P. J., Buxbaum, J. D., Jarvik, G. P., Crane, P. K., et al. (2011) · Nature Genetics · doi:10.1038/ng.801 · Cited by 1,901 · see citing works
Self-citationIntegrated 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
Bouchon, A., Dietrich, J., & Colonna, M. (2000) · The Journal of Immunology · doi:10.4049/jimmunol.164.10.4991 · Cited by 1,284 · cited 6× · see citing works
“Our exon-level analysis of CD33 expression highlights an emerging role for an infiltrating macrophage and/or microglial activation network (including the genes TYROBP, CD33 and TREM2) in modulating AD susceptibility and pathology.”
BackgroundInfluentialAlzheimer’s Disease Risk Gene CD33 Inhibits Microglial Uptake of Amyloid Beta
Griciuc, A., Serrano-Pozo, A., Parrado, A. R., Lesinski, A. N., Asselin, C. N., Mullin, K., Hooli, B., Choi, S. H., Hyman, B. T., & Tanzi, R. E. (2013) · Neuron · doi:10.1016/j.neuron.2013.04.014 · Cited by 1,004 · see citing works
Overview and Findings from the Rush Memory and Aging Project
Bennett, D. A., Schneider, J. A., Buchman, A. S., Barnes, L. L., Boyle, P. A., & Wilson, R. S. (2012) · Current Alzheimer Research · doi:10.2174/156720512801322663 · Cited by 837 · see citing works
Han, B., & Eskin, E. (2011) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2011.04.014 · Cited by 680 · see citing works
Overview and Findings from the Religious Orders Study
Bennett, D. A., Schneider, J. A., Arvanitakis, Z., & Wilson, R. S. (2012) · Current Alzheimer Research · doi:10.2174/156720512801322573 · Cited by 647 · see citing works
CD33 Alzheimer's disease locus: altered monocyte function and amyloid biology
Initiative, T. A. D. N., Bradshaw, E. M., Chibnik, L. B., Keenan, B. T., Ottoboni, L., Raj, T., Tang, A., Rosenkrantz, L. L., Imboywa, S., Lee, M., et al. (2013) · Nature Neuroscience · doi:10.1038/nn.3435 · Cited by 570 · see citing works
Self-citationBertram, L., Lange, C., Mullin, K., Parkinson, M., Hsiao, M., Hogan, M. F., Schjeide, B. M. M., Hooli, B., DiVito, J., Ionita, I., et al. (2008) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2008.10.008 · Cited by 511 · see citing works
Reitz, C., Jun, G., Naj, A., Rajbhandary, R., Vardarajan, B. N., Wang, L.-S., Valladares, O., Lin, C.-F., Larson, E. B., Graff-Radford, N. R., et al. (2013) · JAMA · doi:10.1001/jama.2013.2973 · Cited by 431 · see citing works
Nica, A. C., Montgomery, S. B., Dimas, A. S., Stranger, B. E., Beazley, C., Barroso, I., & Dermitzakis, E. T. (2010) · PLoS Genetics · doi:10.1371/journal.pgen.1000895 · Cited by 423 · see citing works
Genomewide Analysis of mRNA Processing in Yeast Using Splicing-Specific Microarrays
Clark, T. A., Sugnet, C. W., & Ares, M. (2002) · Science · doi:10.1126/science.1069415 · Cited by 411 · see citing works
CD33 Alzheimer’s risk-altering polymorphism, CD33 expression, and exon 2 splicing
Malik, M., Simpson, J. F., Parikh, I., Wilfred, B. R., Fardo, D. W., Nelson, P. T., & Estus, S. (2013) · The Journal of Neuroscience · doi:10.1523/jneurosci.1224-13.2013 · Cited by 262 · see citing works
A Comprehensive Genetic Association Study of Alzheimer Disease in African Americans
Logue, M. W. (2011) · Archives of Neurology · doi:10.1001/archneurol.2011.646 · Cited by 250 · see citing works
Genome-wide association study of Alzheimer's disease
Kamboh, M. I., Demirci, F. Y., Wang, X., Minster, R. L., Carrasquillo, M. M., Pankratz, V. S., Younkin, S. G., Saykin, A. J., Initiative, A. D. N., Jun, G., et al. (2012) · Translational Psychiatry · doi:10.1038/tp.2012.45 · Cited by 242 · see citing works
Hernández‐Caselles, T., Martinez‐Esparza, M., Pérez‐Oliva, A. B., Quintanilla-Cecconi, A. M., García-Alonso, A. M., Álvarez‐López, D. M. R., & García–Peñarrubia, P. (2005) · Journal of Leukocyte Biology · doi:10.1189/jlb.0205096 · Cited by 133 · see citing works
Identification of cis-regulatory variation influencing protein abundance levels in human plasma
Lourdusamy, A., Newhouse, S., Lunnon, K., Proitsi, P., Powell, J. F., Hodges, A., Nelson, S. K., Stewart, A., Williams, S. A., Kłoszewska, I., et al. (2012) · Human Molecular Genetics · doi:10.1093/hmg/dds186 · Cited by 84 · see citing works
Carrasquillo, M. M., Belbin, O., Hunter, T. A., Ma, L., Bisceglio, G. D., Zou, F., Crook, J. E., Pankratz, V. S., Sando, S. B., Aasly, J. O., et al. (2011) · Molecular Neurodegeneration · doi:10.1186/1750-1326-6-54 · Cited by 82 · see citing works
Association of GWAS Top Hits With Late-onset Alzheimer Disease in Korean Population
Chung, S. J., Lee, J., Kim, S. Y., You, S., Kim, M. J., Lee, J., & Koh, J. (2012) · Alzheimer Disease & Associated Disorders · doi:10.1097/wad.0b013e31826d7281 · Cited by 74 · see citing works
Microglia as Dynamic and Essential Components of the Amyloid Hypothesis
Gandy, S., & Heppner, F. L. (2013) · Neuron · doi:10.1016/j.neuron.2013.05.007 · Cited by 73 · see citing works
The prevalence of CD33 and MS4A6A variant in Chinese Han population with Alzheimer’s disease
Deng, Y., Liu, L., Wang, Y., Tang, H., Ren, R., Xu, W. L., Ma, J., Wang, L., Zhuang, J.-P., Wang, G., et al. (2012) · Human Genetics · doi:10.1007/s00439-012-1154-6 · Cited by 54 · see citing works
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Microglia in Alzheimer’s disease
Hansen, D. V., Hanson, J. E., & Sheng, M. (2018) · Journal of Cell Biology · doi:10.1083/jcb.201709069 · Cited by 1,935 · see citing works
“A combined analysis of neuroimaging and genetic data found an association between a polymorphism in the IL1RAP gene and increased rate of Aβ accumulation in human brains of both AD and non-AD subjects (measured by Aβ-binding positron emission tomography tracer; Ramanan et al., 2015).”
BackgroundReligious Orders Study and Rush Memory and Aging Project
Bennett, D. A., Buchman, A. S., Boyle, P. A., Barnes, L. L., Wilson, R. S., & Schneider, J. A. (2018) · Journal of Alzheimer's Disease · doi:10.3233/jad-179939 · Cited by 1,260 · see citing works
Siglec-mediated regulation of immune cell function in disease
Macauley, M. S., Crocker, P. R., & Paulson, J. C. (2014) · Nature Reviews Immunology · doi:10.1038/nri3737 · Cited by 1,098 · see citing works
Schwartzentruber, J., Cooper, S., Liu, J. Z., Barrio-Hernandez, I., Bello, E., Kumasaka, N., Young, A. M. H., Franklin, R. J. M., Johnson, T., Estrada, K., et al. (2021) · Nature Genetics · doi:10.1038/s41588-020-00776-w · Cited by 532 · see citing works
Inflammation: the link between comorbidities, genetics, and Alzheimer’s disease
Newcombe, E. A., Camats-Perna, J., Silva, M. L., Valmas, N., Huat, T. J., & Medeiros, R. (2018) · Journal of Neuroinflammation · doi:10.1186/s12974-018-1313-3 · Cited by 532 · see citing works
Siglecs as Immune Cell Checkpoints in Disease
Duan, S., & Paulson, J. C. (2020) · Annual Review of Immunology · doi:10.1146/annurev-immunol-102419-035900 · Cited by 452 · see citing works
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
Cuyvers, E., & Sleegers, K. (2016) · The Lancet Neurology · doi:10.1016/s1474-4422(16)00127-7 · Cited by 284 · see citing works
Fernandez, C. G., Hamby, M. E., McReynolds, M. L., & Ray, W. J. (2019) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2019.00014 · Cited by 277 · see citing works
Lopes, K. D. P., Snijders, G. J. L., Humphrey, J., Allan, A., Sneeboer, M. A. M., Navarro, E., Schilder, B. M., Vialle, R. A., Parks, M., Missall, R., et al. (2022) · Nature Genetics · doi:10.1038/s41588-021-00976-y · Cited by 273 · see citing works
Self-citationA Map of Transcriptional Heterogeneity and Regulatory Variation in Human Microglia
Young, A. M. H., Kumasaka, N., Calvert, F., Hammond, T. R., Knights, A., Panousis, N., Park, J. S., Schwartzentruber, J., Liu, J., Kundu, K., et al. (2021) · Nature Genetics · doi:10.1038/s41588-021-00875-2 · Cited by 213 · see citing works
Untangling Genetic Risk for Alzheimer’s Disease
Pimenova, A. A., Raj, T., & Goate, A. M. (2018) · Biological Psychiatry · doi:10.1016/j.biopsych.2017.05.014 · Cited by 223 · see citing works
Microglial Phagocytosis: A Disease-Associated Process Emerging from Alzheimer’s Disease Genetics
Podleśny-Drabiniok, A., Marcora, E., & Goate, A. M. (2020) · Trends in Neurosciences · doi:10.1016/j.tins.2020.10.002 · Cited by 211 · see citing works
Gemtuzumab ozogamicin in acute myeloid leukemia
Godwin, C. D., Gale, R. P., & Walter, R. B. (2017) · Leukemia · doi:10.1038/leu.2017.187 · Cited by 211 · see citing works
Genetics of Alzheimer’s Disease
Chouraki, V. A., & Seshadri, S. S. (2014) · Advances in genetics · doi:10.1016/b978-0-12-800149-3.00005-6 · Cited by 208 · see citing works
The role of innate immune genes in Alzheimer's disease
Griciuc, A., & Tanzi, R. E. (2021) · Current Opinion in Neurology · doi:10.1097/wco.0000000000000911 · Cited by 191 · see citing works
Targeting microglia for the treatment of Alzheimer’s Disease
Wes, P. D., Sayed, F. A., Bard, F., & Gan, L. (2016) · Glia · doi:10.1002/glia.22988 · Cited by 185 · see citing works
CD33 modulates TREM2: convergence of Alzheimer loci
Chan, G., White, C. C., Winn, P. A., Cimpean, M., Replogle, J. M., Glick, L. R., Cuerdon, N. E., Ryan, K. J., Johnson, K. A., Schneider, J. A., et al. (2015) · Nature Neuroscience · doi:10.1038/nn.4126 · Cited by 162 · see citing works
Genetics ignite focus on microglial inflammation in Alzheimer’s disease
Malik, M., Parikh, I., Vasquez, J. B., Smith, C., Tai, L., Bu, G., LaDu, M. J., Fardo, D. W., Rebeck, G. W., & Estus, S. (2015) · Molecular Neurodegeneration · doi:10.1186/s13024-015-0048-1 · Cited by 161 · see citing works
Ryan, K. J., White, C. C., Patel, K. R., Xu, J., Olah, M., Replogle, J. M., Frangieh, M., Cimpean, M., Winn, P. A., McHenry, A., et al. (2017) · Science Translational Medicine · doi:10.1126/scitranslmed.aai7635 · Cited by 156 · see citing works
Lamba, J. K., Chauhan, L., Shin, M., Loken, M. R., Pollard, J. A., Wang, Y.-C., Ries, R. E., Aplenc, R., Hirsch, B. A., Raimondi, S. C., et al. (2017) · Journal of Clinical Oncology · doi:10.1200/jco.2016.71.2513 · Cited by 157 · see citing works
Prioritizing Parkinson’s disease genes using population-scale transcriptomic data
Li, Y. I., Wong, G., Humphrey, J., & Raj, T. (2019) · Nature Communications · doi:10.1038/s41467-019-08912-9 · Cited by 153 · see citing works
Sialylation and Galectin-3 in Microglia-Mediated Neuroinflammation and Neurodegeneration
Puigdellívol, M., Allendorf, D. H., & Brown, G. C. (2020) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2020.00162 · Cited by 145 · see citing works
Piirainen, S., Youssef, A. M., Song, C., Kalueff, A. V., Landreth, G. E., Malm, T., & Tian, L. (2017) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2017.01.046 · Cited by 125 · see citing works
CD33 in Alzheimer’s Disease – Biology, Pathogenesis, and Therapeutics: A Mini-Review
Zhao, L. (2018) · Gerontology · doi:10.1159/000492596 · Cited by 124 · see citing works
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Siddiqui, S. S., Matar, R., Merheb, M., Hodeify, R., Vazhappilly, C. G., Marton, J., Shamsuddin, S. A., & Al Zouabi, H. (2019) · Cells · doi:10.3390/cells8101125 · Cited by 100 · see citing works
Therapeutic Targeting of Siglecs using Antibody- and Glycan-Based Approaches
Angata, T., Nycholat, C. M., & Macauley, M. S. (2015) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2015.06.008 · Cited by 97 · see citing works
Repression of phagocytosis by human CD33 is not conserved with mouse CD33
Bhattacherjee, A., Rodrigues, E., Jung, J., Luzentales-Simpson, M., Enterina, J. R., Galleguillos, D., Laurent, C. D. S., Nakhaei‐Nejad, M., Fuchsberger, F. F., Streith, L., et al. (2019) · Communications Biology · doi:10.1038/s42003-019-0698-6 · Cited by 97 · see citing works
Evaluation of CD33 as a genetic risk factor for Alzheimer’s disease
Estus, S., Shaw, B. C., Devanney, N. A., Katsumata, Y., Press, E., & Fardo, D. W. (2019) · Acta Neuropathologica · doi:10.1007/s00401-019-02000-4 · Cited by 95 · see citing works
Walker, D. G., Whetzel, A. M., Serrano, G., Sue, L. I., Beach, T. G., & Lue, L.-F. (2015) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2014.09.023 · Cited by 93 · see citing works
Neuroinflammation as a Potential Therapeutic Target in Alzheimer’s Disease
Liu, P., Wang, Y., Sun, Y., & Peng, G. (2022) · Clinical Interventions in Aging · doi:10.2147/cia.s357558 · Cited by 92 · see citing works
Deletion of Alzheimer's disease‐associated CD33 results in an inflammatory human microglia phenotype
Wißfeld, J., Nozaki, I., Mathews, M., Raschka, T., Ebeling, C., Hornung, V., Brüstle, O., & Neumann, H. (2021) · Glia · doi:10.1002/glia.23968 · Cited by 89 · see citing works
Genetics of CD33 in Alzheimer's disease and acute myeloid leukemia
Malik, M., Chiles, J. W., Xi, H. S., Medway, C., Simpson, J. F., Potluri, S., Howard, D. S., Yu, L., Paumi, C. M., Mukherjee, S., et al. (2015) · Human Molecular Genetics · doi:10.1093/hmg/ddv092 · Cited by 82 · see citing works
A TREM 1 variant alters the accumulation of Alzheimer‐related amyloid pathology
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Discovery, classification, evolution and diversity of Siglecs
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Miles, L. A., Hermans, S. J., Crespi, G. A. N., Gooi, J. H., Doughty, L., Nero, T. L., Markulić, J., Ebneth, A., Wroblowski, B., Oehlrich, D., et al. (2019) · iScience · doi:10.1016/j.isci.2019.07.023 · Cited by 81 · see citing works
Alternative splicing in Alzheimer’s disease
Biamonti, G., Amato, A. M., Belloni, E., Matteo, A. D., Infantino, L., Pradella, D., & Ghigna, C. (2019) · Aging Clinical and Experimental Research · doi:10.1007/s40520-019-01360-x · Cited by 77 · see citing works
The CD33 short isoform is a gain-of-function variant that enhances Aβ1–42 phagocytosis in microglia
Bhattacherjee, A., Jung, J., Zia, S., Ho, M. F. S., Eskandari‐Sedighi, G., Laurent, C. D. S., McCord, K. A., Bains, A., Sidhu, G., Sarkar, S., et al. (2021) · Molecular Neurodegeneration · doi:10.1186/s13024-021-00443-6 · Cited by 76 · see citing works
Schwarz, F., Springer, S. A., Altheide, T. K., Varki, N. M., Gagneux, P., & Varki, A. P. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1517951112 · Cited by 71 · see citing works
Current views on meningeal lymphatics and immunity in aging and Alzheimer’s disease
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CD33 isoforms in microglia and Alzheimer's disease: Friend and foe
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Ye, C., Chen, J., Villani, A., Gate, R. E., Subramaniam, M., Bhangale, T., Lee, M. N., Raj, T., Raychowdhury, R., Li, W., et al. (2018) · Genome Research · doi:10.1101/gr.240390.118 · Cited by 67 · see citing works
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Brown, G. D., & Crocker, P. R. (2016) · Microbiology Spectrum · doi:10.1128/microbiolspec.mchd-0036-2016 · Cited by 66 · see citing works
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Bennett, D. A., Yu, L., & Jager, P. L. D. (2014) · Biochemical Pharmacology · doi:10.1016/j.bcp.2014.01.037 · Cited by 53 · see citing works
Laszlo, G. S., Harrington, K. H., Gudgeon, C. J., Beddoe, M. E., Fitzgibbon, M., Ries, R. E., Lamba, J. K., McIntosh, M. W., Meshinchi, S., & Walter, R. B. (2016) · Oncotarget · doi:10.18632/oncotarget.9674 · Cited by 57 · see citing works
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Son, M., Diamond, B., Volpe, B. T., Aranow, C. B., Mackay, M. C., & Santiago‐Schwarz, F. (2017) · Scientific Reports · doi:10.1038/s41598-017-00290-w · Cited by 55 · see citing works
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Li, X., Shen, N., Zhang, S., Liu, J., Jiang, Q., Liao, M., Feng, R., Zhang, L., Wang, G., Ma, G., et al. (2014) · Molecular Neurobiology · doi:10.1007/s12035-014-8880-9 · Cited by 49 · see citing works
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Sudwarts, A., & Thinakaran, G. (2023) · Molecular Neurodegeneration · doi:10.1186/s13024-023-00679-4 · Cited by 46 · see citing works
Alzheimer’s disease: rare variants with large effect sizes
Del-Aguila, J. L., Koboldt, D. C., Black, K., Chasse, R., Norton, J., Wilson, R. K., & Cruchaga, C. (2015) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2015.07.008 · Cited by 41 · see citing works
Nair-Gupta, P., Diem, M. D., Reeves, D. A., Wang, W., Schulingkamp, R. J., Sproesser, K., Mattson, B. K., Heidrich, B. J., Mendonça, M., Joseph, J., et al. (2020) · Blood Advances · doi:10.1182/bloodadvances.2019001188 · Cited by 41 · see citing works
Human-Specific Evolutionary Changes in the Biology of Siglecs
Schwarz, F., Fong, J. J., & Varki, A. P. (2014) · Advances in experimental medicine and biology · doi:10.1007/978-3-319-11280-0_1 · Cited by 40 · see citing works
Possible Influences of Endogenous and Exogenous Ligands on the Evolution of Human Siglecs
Angata, T. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.02885 · Cited by 40 · see citing works
Gao, C., Shen, X., Tan, Y., & Chen, S. (2022) · Journal of Neuroinflammation · doi:10.1186/s12974-022-02580-1 · Cited by 43 · see citing works
Associations of genetic polymorphisms of Siglecs with human diseases
Angata, T. (2014) · Glycobiology · doi:10.1093/glycob/cwu043 · Cited by 38 · see citing works
Role of Microglia in Regulating Cholesterol and Tau Pathology in Alzheimer’s Disease
Nanjundaiah, S., Chidambaram, H., Chandrashekar, M., & Chinnathambi, S. (2020) · Cellular and Molecular Neurobiology · doi:10.1007/s10571-020-00883-6 · Cited by 36 · see citing works
van Bergeijk, P., Seneviratne, U. I., Aparicio-Prat, E., Stanton, R. V., & Hasson, S. A. (2019) · Molecular and Cellular Biology · doi:10.1128/mcb.00568-18 · Cited by 36 · see citing works
Microglial Drug Targets in AD: Opportunities and Challenges in Drug Discovery and Development
Biber, K., Bhattacharya, A., Campbell, B. M., Piro, J. R., Rohe, M., Staal, R. G. W., Talanian, R. V., & Möller, T. (2019) · Frontiers in Pharmacology · doi:10.3389/fphar.2019.00840 · Cited by 37 · see citing works
Small molecule targeting of SHIP1 and SHIP2
Kerr, W. G., Pedicone, C., Dormann, S., Pacherille, A., & Chisholm, J. D. (2020) · Biochemical Society Transactions · doi:10.1042/bst20190775 · Cited by 36 · see citing works
Biomarkers of Gemtuzumab Ozogamicin Response for Acute Myeloid Leukemia Treatment
Fenwarth, L., Fournier, É., Cheok, M. H.-C., Boyer, T., Gonzales, F., Castaigné, S., Boissel, N., Lambert, J., Dombret, H., Preudhomme, C., et al. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21165626 · Cited by 36 · see citing works
CELF2 regulates the species-specific alternative splicing of TREM2
Yanaizu, M., Washizu, C., Nukina, N., Satoh, J., & Kino, Y. (2020) · Scientific Reports · doi:10.1038/s41598-020-75057-x · Cited by 32 · see citing works
Humphrey, J., Brophy, E., Kosoy, R., Zeng, B., Coccia, E., Mattei, D., Ravi, A., Naito, T., Efthymiou, A. G., Navarro, E., et al. (2025) · Nature Genetics · doi:10.1038/s41588-025-02099-0 · Cited by 36 · see citing works
Gemtuzumab Ozogamicin for Treatment of Newly Diagnosed CD33-Positive Acute Myeloid Leukemia
Gbadamosi, M. O., Meshinchi, S., & Lamba, J. K. (2018) · Future Oncology · doi:10.2217/fon-2018-0325 · Cited by 34 · see citing works
Eskandari‐Sedighi, G., Crichton, M. C., Zia, S., Gomez‐Cardona, E., Cortez, L. M., Patel, Z. H., Takahashi, K., Laurent, C. D. S., Sidhu, G., Sarkar, S., et al. (2024) · Molecular Neurodegeneration · doi:10.1186/s13024-024-00734-8 · Cited by 35 · see citing works
Therapeutics of Alzheimer’s Disease: Recent Developments
Burns, S., Selman, A., Sehar, U., Rawat, P., Reddy, A. P., & Reddy, P. H. (2022) · Antioxidants · doi:10.3390/antiox11122402 · Cited by 31 · see citing works
Microglia and its Genetics in Alzheimer's Disease
Liang, X., Wu, H., Colt, M., Guo, X., Pluimer, B. R., Zeng, J., Dong, S., & Zhao, Z. (2021) · Current Alzheimer Research · doi:10.2174/1567205018666211105140732 · Cited by 31 · see citing works
Genetic insights into immune mechanisms of Alzheimer’s and Parkinson’s disease
Nott, A., & Holtman, I. R. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1168539 · Cited by 31 · see citing works
Trans -pQTL study identifies immune crosstalk between Parkinson and Alzheimer loci
Chan, G., White, C. C., Winn, P. A., Cimpean, M., Replogle, J. M., Glick, L. R., Cuerdon, N., Ryan, K. J., Johnson, K. A., Schneider, J. A., et al. (2016) · Neurology Genetics · doi:10.1212/nxg.0000000000000090 · Cited by 28 · see citing works
Yan, H., Wang, W., Cui, T., Shao, Y., Li, M., Fang, L., & Feng, L. (2024) · ImmunoTargets and Therapy · doi:10.2147/itt.s455881 · Cited by 30 · see citing works
Ramdhani, S., Navarro, E., Udine, E., Efthymiou, A. G., Schilder, B. M., Parks, M., Goate, A., & Raj, T. (2020) · PLoS Genetics · doi:10.1371/journal.pgen.1008549 · Cited by 26 · see citing works
Alzheimer’s Disease Treatment: The Search for a Breakthrough
Reiss, A. B., Muhieddine, D., Jacob, B., Mesbah, M., Pinkhasov, A., Gomolin, I. H., Stecker, M. M., Wısnıewskı, T., & Leon, J. D. (2023) · Medicina · doi:10.3390/medicina59061084 · Cited by 29 · see citing works
Immune dysfunction in Alzheimer disease
Butovsky, O., Rosenzweig, N., Kleemann, K. L., Jorfi, M., Kuchroo, V. K., Tanzi, R. E., & Weiner, H. L. (2025) · Nature reviews. Neuroscience · doi:10.1038/s41583-025-00997-0 · Cited by 34 · see citing works
Li, S., Weinstein, G., Zare, H., Teumer, A., Völker, U., Friedrich, N., Knol, M. J., Satizábal, C. L., Petyuk, V., Adams, H. H. H., et al. (2020) · Brain Communications · doi:10.1093/braincomms/fcaa176 · Cited by 26 · see citing works
Kiianitsa, K., Kurtz, I., Beeman, N. E., Matsushita, M. M., Chien, W., Raskind, W. H., & Korvatska, O. (2021) · Journal of Leukocyte Biology · doi:10.1002/jlb.2hi0720-463rr · Cited by 25 · see citing works
Alzheimer’s Disease: Models and Molecular Mechanisms Informing Disease and Treatments
Nystuen, K., McNamee, S. M., Akula, M., Holton, K. M., DeAngelis, M. M., & Haider, N. B. (2024) · Bioengineering · doi:10.3390/bioengineering11010045 · Cited by 16 · see citing works
Felsky, D., Santa‐María, I., Coşacak, M. İ., French, L., Schneider, J. A., Bennett, D. A., Jager, P. L. D., Kızıl, Ç., & Tosto, G. (2022) · Neurobiology of Disease · doi:10.1016/j.nbd.2022.105938 · Cited by 25 · see citing works
Bao, J., Wang, X., & Mao, Z.-F. (2016) · Medical Science Monitor · doi:10.12659/msm.895622 · Cited by 24 · see citing works
CD33 rs2455069 SNP: Correlation with Alzheimer’s Disease and Hypothesis of Functional Role
Tortora, F., Rendina, A., Angiolillo, A., Costanzo, A. D., Aniello, F., Donizetti, A., Febbraio, F., & Vitale, E. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23073629 · Cited by 22 · see citing works
He, L., Loika, Y., & Kulminski, A. M. (2022) · Translational Psychiatry · doi:10.1038/s41398-022-01913-1 · Cited by 22 · see citing works
Pathways linking Alzheimer’s disease risk genes expressed highly in microglia
Hodges, A. K., Piers, T. M., Collier, D., Cousins, O., & Pocock, J. M. (2021) · Neuroimmunology and Neuroinflammation · doi:10.20517/2347-8659.2020.60 · Cited by 21 · see citing works
Roles of Siglecs in neurodegenerative diseases
Siew, J. J., Chern, Y., Khoo, K., & Angata, T. (2022) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2022.101141 · Cited by 20 · see citing works
The CD33 splice isoform lacking exon 2 as therapeutic target in human acute myeloid leukemia
Godwin, C. D., Laszlo, G. S., Wood, B. L., Correnti, C., Bates, O. M., Garling, E. E., Mao, Z. J., Beddoe, M. E., Lunn-Halbert, M. C., Humbert, O., et al. (2020) · Leukemia · doi:10.1038/s41375-020-0755-7 · Cited by 21 · see citing works
Therapeutic Targeting of Acute Myeloid Leukemia by Gemtuzumab Ozogamicin
Gottardi, M., Simonetti, G., Sperotto, A. A., Nappi, D., di Rorà, A. G. L., Padella, A., Norata, M., Giannini, M. B., Musuraca, G., Lanza, F., et al. (2021) · Cancers · doi:10.3390/cancers13184566 · Cited by 20 · see citing works
Alzheimer’s Disease Genetics: A Dampened Microglial Response?
Chatila, Z. K., & Bradshaw, E. M. (2021) · The Neuroscientist · doi:10.1177/10738584211024531 · Cited by 20 · see citing works
TREM2 variants that cause early dementia and increase Alzheimer’s disease risk affect gene splicing
Kiianitsa, K., Lukes, M. E., Hayes, B. J., Brutman, J. N., Valdmanis, P. N., Bird, T. D., Raskind, W. H., & Korvatska, O. (2024) · Brain · doi:10.1093/brain/awae014 · Cited by 18 · see citing works
Blumenau, S., Foddis, M., Müller, S., Holtgrewe, M., Bentele, K., Berchtold, D., Beule, D., Dirnagl, U., & Sassi, C. (2020) · Scientific Reports · doi:10.1038/s41598-020-63183-5 · Cited by 18 · see citing works
Gemtuzumab ozogamicin in acute myeloid leukemia: past, present and future
Gottardi, M., Sperotto, A. A., di Rorà, A. G. L., Padella, A., Cangini, D., Giannini, M. B., Simonetti, G., Martinelli, G., & Cerchione, C. (2020) · Minerva Medica · doi:10.23736/s0026-4806.20.07019-6 · Cited by 18 · see citing works
Discovery of Small-Molecule CD33 Pre-mRNA Splicing Modulators
Chappie, T. A., Abdelmessih, M., Ambroise, C., Boehm, M., Cai, M., Green, M., Guilmette, E. R., Steppan, C. M., Stevens, L. M., Wei, L., et al. (2022) · ACS Medicinal Chemistry Letters · doi:10.1021/acsmedchemlett.1c00396 · Cited by 17 · see citing works
Wong, E., Malviya, M., Jain, T., Liao, G. P., Kehs, Z., Chang, J. C., Studer, L., Scheinberg, D. A., & Li, Y. (2024) · Molecular Psychiatry · doi:10.1038/s41380-024-02474-z · Cited by 16 · see citing works
Pramanik, S., Harini Devi, M., Chakrabarty, S., Paylar, B., Pradhan, A., Thaker, M., Ayyadhury, S., Manavalan, A., Olsson, P., Pramanik, G., et al. (2024) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2024.105834 · Cited by 18 · see citing works
Multiple Sclerosis: Shall We Target CD33?
Siokas, V., Tsouris, Z., Aloizou, A., Bakirtzis, C., Liampas, I., Koutsis, G., Anagnostouli, M. C., Bogdanos, D. P., Grigoriadis, N., Hadjigeorgiou, G. M., et al. (2020) · Genes · doi:10.3390/genes11111334 · Cited by 15 · see citing works
Missing lnc(RNAs) in Alzheimer’s Disease?
Policarpo, R., & d’Ydewalle, C. V. O. (2021) · Genes · doi:10.3390/genes13010039 · Cited by 14 · see citing works
Lopes, K. P., Snijders, G. J. L., Humphrey, J., de Witte, L. D., & Raj, T. (2021) · Alzheimer s & Dementia · doi:10.1002/alz.050942 · Cited by 17 · see citing works
Komuro, R., Honda, Y., Yanaizu, M., Nagahama, M., & Kino, Y. (2023) · Cells · doi:10.3390/cells12040602 · Cited by 13 · see citing works
The relationship of early- and late-onset Alzheimer’s disease genes with COVID-19
Şirin, S., Dolanbay, S. N., & Aslım, B. (2022) · Journal of Neural Transmission · doi:10.1007/s00702-022-02499-0 · Cited by 13 · see citing works
- Authors
- Raj, T., Ryan, K. J., Replogle, J. M., Chibnik, L. B., Rosenkrantz, L., Tang, A., Rothamel, K., Stranger, B. E., Bennett, D. A., Evans, D. A., De Jager, P. L., & Bradshaw, E. M.
- Affiliations
- Broad Institute (US)
- Brigham and Women's Hospital (US)
- University of Chicago (US)
- Rush University Medical Center (US)
- Corresponding author
- Bradshaw, E. M.
- ORCID
- Venue
- Human Molecular Genetics
- Publisher
- Oxford University Press (OUP)
- Published
- 2013-12-30
- Volume
- 23
- Issue
- 10
- Pages
- 2729-2736
- ISSN
- 0964-6906 (ISSN-L)
- 1460-2083
- PMC
- PMC3990171
- OpenAlex
- W2161428211
- Cited by
- 144
- References
- 27
- Citations by year
- 2026: 3 · 2025: 7 · 2024: 13 · 2023: 10 · 2022: 18 · 2021: 20 · 2020: 18 · 2019: 13 · 2018: 9 · 2017: 9 · 2016: 9 · 2015: 7 · 2014: 8
- FWCI
- 5.56
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Human Molecular Genetics (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute on Aging (R01AG017917, P30-AG 10161, K25AG041906, R01AG030146, R01 AG30146, R01‐AG17917, R01 AG15819, R01AG11101, R01AG011101, R01AG043617, R01AG015819, P30AG010161, F32AG043267, R01AG031553)
- National Institute of General Medical Sciences (RC2GM093080)
- National Institute of Neurological Disorders and Stroke (R01NS067305)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Keywords
- CD33, Alzheimer's disease, alternative splicing, exon 2, monocytes, cell surface expression, haplotypes, linkage disequilibrium, SRSF2, genetic susceptibility, CD14+CD16+ monocytes
- MeSH terms
- Alzheimer Disease, Black or African American, Exons, Humans, Linkage Disequilibrium, Case-Control Studies, Alternative Splicing, Sequence Analysis, DNA, Protein Structure, Tertiary, Genetic Predisposition to Disease, Protein Isoforms, Polymorphism, Single Nucleotide, White People, Genetic Association Studies, Sialic Acid Binding Ig-like Lectin 3
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