Alzheimer risk associated with a copy number variation in the complement receptor 1 increasing C3b/C4b binding sites
Open accessAbstract
Two multicentre genome-wide association (GWA) studies provided substantial evidence, implicating the complement receptor 1 gene (CR1) in Alzheimer disease (AD) genetic etiology. CR1 encodes a large transmembrane receptor with a crucial role in the immune complement cascade. We performed a genetic follow-up of the GWA CR1 association in a Flanders-Belgian cohort (n=1883), and investigated the effect of single-nucleotide polymorphisms (SNPs) located in the CR1 locus on AD risk and cerebrospinal fluid (CSF) biomarker levels. We obtained significant association (P(adj)<0.03; odds ratio (OR)=1.24 (95% confidence interval (CI): 1.02-1.51)) for one CR1 risk haplotype, and haplotype association was strongest in individuals carrying apolipoprotein E (APOE) ɛ4 alleles (P(adj)<0.006; OR=1.50 (95% CI: 1.08-2.09)). Also, four SNPs correlated with increased CSF amyloid Aβ₁₋₄₂ levels, suggesting a role for the CR1 protein in Aβ metabolism. Moreover, we quantified a low-copy repeat (LCR)-associated copy number variation (CNV) in CR1, producing different CR1 isoforms, CR1-F and CR1-S, and obtained significant association in carriers of CR1-S. We replicated the CR1 CNV association finding in a French cohort (n=2003) and calculated in the combined cohorts, an OR of 1.32; 95% CI: 1.10-1.59 (P=0.0025). Our data showed that the common AD risk association may well be explained by the presence of CR1-S increasing the number of C3b/C4b and cofactor activity sites and AD risk with 30% in CR1-S carriers. How precisely the different functional role of CR1-S in the immune complement cascade contributes to AD pathogenesis will need additional functional studies.
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?
The analyses nominate alternative candidates at three AD risk loci: CR2 at 1q32.2, PILRA at 7q22.1, and PRSS8 at 16p11.2.
“Our analyses also nominate alternative candidates at three AD risk loci. First, the association at 1q32.2 has been linked to CR153–55, but we observed a colocalized association for both CR1 and CR2 levels with AD risk (Supp. Fig. 23).”
From Proteogenomic analysis of human cerebrospinal fluid identifies neurologically relevant regulation and implicates causal proteins for Alzheimer’s disease (2024) · cites this paper as [55]
SCFAs, as important metabolites of the intestinal flora, can modulate the immune response and act as important communication signals on the brain-gut axis.
“SCFAs, as important metabolites of the intestinal flora, can modulate the immune response (38) and act as important communication signals on the brain–gut axis (39).”
From Modulation of the gut–brain axis via the gut microbiota: a new era in treatment of amyotrophic lateral sclerosis (2023) · cites this paper as [39]
A functional CNV in the gene CR1 modifying isoform production was shown to increase risk for LOAD in two populations.
“a functional CNV in the gene CR1 modifying isoform production was shown to increase risk for LOAD in two populations [253]”
From Genetic architecture of Alzheimer's disease (2020) · cites this paper as [253]
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
McKhann, G., Drachman, D., Folstein, M., Katzman, R., Price, D., & Stadlan, E. M. (1984) · Neurology · doi:10.1212/wnl.34.7.939 · Cited by 27,915 · see citing works
Haploview: analysis and visualization of LD and haplotype maps
Barrett, J., Fry, B., Maller, J., & Daly, M. (2005) · Bioinform. · doi:10.1093/bioinformatics/bth457 · Cited by 15,086 · 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
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
Self-citationGenome-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
Self-citationComplement and its role in innate and adaptive immune responses
Dunkelberger, J. R., & Song, W.-C. (2010) · Cell Research · doi:10.1038/cr.2009.139 · Cited by 1,932 · see citing works
Score Tests for Association between Traits and Haplotypes when Linkage Phase Is Ambiguous
Schaid, D. J., Rowland, C. M., Tines, D. E., Jacobson, R. M., & Poland, G. A. (2002) · The American Journal of Human Genetics · doi:10.1086/338688 · Cited by 1,772 · see citing works
Complement activation by beta-amyloid in Alzheimer disease.
Rogers, J., Cooper, N. R., Webster, S., Schultz, J., McGeer, P. L., Styren, S. D., Civin, W. H., Brachova, L., Bradt, B., & Ward, P. (1992) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.89.21.10016 · Cited by 817 · see citing works
Shin, J., Blay, S., Graham, J., & McNeney, B. (2006) · Journal of Statistical Software · doi:10.18637/jss.v016.c03 · Cited by 643 · see citing works
Prominent neurodegeneration and increased plaque formation in complement-inhibited Alzheimer's mice
Wyss-Coray, T., Yan, F., Lin, A. H.-T., Lambris, J. D., Alexander, J. J., Quigg, R. J., & Masliah, E. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.162350199 · Cited by 446 · see citing works
Absence of C1q Leads to Less Neuropathology in Transgenic Mouse Models of Alzheimer's Disease
Fonseca, M. I., Zhou, J., Botto, M., & Tenner, A. J. (2004) · The Journal of Neuroscience · doi:10.1523/jneurosci.0901-04.2004 · Cited by 345 · see citing works
Maier, M., Peng, Y., Jiang, L., Seabrook, T. J., Carroll, M. C., & Lemere, C. A. (2008) · Journal of Neuroscience · doi:10.1523/jneurosci.0829-08.2008 · Cited by 323 · see citing works
A Polymorphism in CALHM1 Influences Ca2+ Homeostasis, Aβ Levels, and Alzheimer's Disease Risk
Dreses‐Werringloer, U., Lambert, J., Vingtdeux, V., Zhao, H., Vais, H., Siebert, A. P., Jain, A., Koppel, J. L., Rovelet‐Lecrux, A., Hannequin, D., et al. (2008) · Cell · doi:10.1016/j.cell.2008.05.048 · Cited by 319 · see citing works
Self-citationKlickstein, L. B., Bartow, T. J., Miletic, V. D., Rabson, L. D., Smith, J. A., & Fearon, D. T. (1988) · The Journal of Experimental Medicine · doi:10.1084/jem.168.5.1699 · Cited by 271 · see citing works
The significance of neuroinflammation in understanding Alzheimer’s disease
Eikelenboom, P., Veerhuis, R., Scheper, W., Rozemüller, A. J. M., van Gool, W. A., & Hoozemans, J. J. M. (2006) · Journal of Neural Transmission · doi:10.1007/s00702-006-0575-6 · Cited by 262 · see citing works
Klickstein, L. B., Wong, W. W., Smith, J. A., Weis, J. H., Wilson, J. G., & Fearon, D. T. (1987) · The Journal of Experimental Medicine · doi:10.1084/jem.165.4.1095 · Cited by 261 · see citing works
Structure–function relationships of complement receptor type 1
Krych‐Goldberg, M., & Atkinson, J. P. (2001) · Immunological Reviews · doi:10.1034/j.1600-065x.2001.1800110.x · Cited by 259 · see citing works
Diagnostic performance of a CSF-biomarker panel in autopsy-confirmed dementia
Engelborghs, S., de Vreese, K., de Casteele, T. V., Vanderstichele, H., Everbroeck, B. V., Cras, P. P., Martin, J., Vanmechelen, E., & Deyn, P. P. D. (2007) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2007.02.016 · Cited by 256 · see citing works
Self-citationComplement-dependent Proinflammatory Properties of the Alzheimer's Disease β-Peptide
Bradt, B. M., Kolb, W. P., & Cooper, N. R. (1998) · The Journal of Experimental Medicine · doi:10.1084/jem.188.3.431 · Cited by 255 · see citing works
Complement Receptor 1: Disease associations and therapeutic implications
Khera, R., & Das, N. (2008) · Molecular Immunology · doi:10.1016/j.molimm.2008.09.026 · Cited by 213 · see citing works
Transcriptomic and genetic studies identify IL-33 as a candidate gene for Alzheimer's disease
Chapuis, J., Hot, D., Hansmannel, F., Kerdraon, O., Ferreira, S., Hubans, C., Maurage, C. A., Huot, L., Bensemain, F., Laumet, G., et al. (2009) · Molecular Psychiatry · doi:10.1038/mp.2009.10 · Cited by 201 · see citing works
Self-citationPeripheral clearance of amyloid β peptide by complement C3-dependent adherence to erythrocytes
Rogers, J., Li, R., Mastroeni, D., Grover, A., Leonard, B., Ahern, G., Cao, P., Kolody, H., Vedders, L., Kolb, W. P., et al. (2006) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2005.09.043 · Cited by 175 · see citing works
Inflammation, the complement system and the diseases of aging
McGeer, E. G., Klegeris, A., & McGeer, P. L. (2005) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2005.08.008 · Cited by 170 · see citing works
Polymorphism of human erythrocyte C3b/C4b receptor.
Dykman, T. R., Cole, J. L., Iida, K., & Atkinson, J. P. (1983) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.80.6.1698 · Cited by 143 · see citing works
Complement C3 and C4 expression in C1q sufficient and deficient mouse models of Alzheimer’s disease
Zhou, J., Fonseca, M. I., Pisalyaput, K., & Tenner, A. J. (2008) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2008.05558.x · Cited by 137 · see citing works
Genetic regulation of a structural polymorphism of human C3b receptor.
Wong, W. W., Wilson, J. G., & Fearon, D. T. (1983) · Journal of Clinical Investigation · doi:10.1172/jci111018 · Cited by 133 · see citing works
The pursuit of susceptibility genes for Alzheimer's disease: progress and prospects
Sleegers, K., Lambert, J.-C., Bertram, L., Cruts, M., Amouyel, P., & Van Broeckhoven, C. (2010) · Trends in Genetics · doi:10.1016/j.tig.2009.12.004 · Cited by 129 · see citing works
Self-citationProspective Belgian study of neurodegenerative and vascular dementia: APOE genotype effects
Engelborghs, S. (2003) · Journal of Neurology Neurosurgery & Psychiatry · doi:10.1136/jnnp.74.8.1148 · Cited by 120 · see citing works
Self-citationWong, W. W., Cahill, J. M., Rosen, M. D., Kennedy, C. A., Bonaccio, E. T., Morris, M. J., Wilson, J. G., Klickstein, L. B., & Fearon, D. T. (1989) · The Journal of Experimental Medicine · doi:10.1084/jem.169.3.847 · Cited by 110 · see citing works
Aggregation State‐Dependent Activation of the Classical Complement Pathway by the Amyloid β Peptide
Webster, S. D., Bradt, B. M., Rogers, J., & Cooper, N. R. (1997) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.1997.69010388.x · Cited by 103 · see citing works
Genetic risk and transcriptional variability of amyloid precursor protein in Alzheimer's disease
Brouwers, N., Sleegers, K., Engelborghs, S., Bogaerts, V., Serneels, S., Kamali, K., Corsmit, E., Leenheir, E. D., Martin, J., Deyn, P. P. D., et al. (2006) · Brain · doi:10.1093/brain/awl212 · Cited by 81 · see citing works
Self-citationHerrera, A. H., Xiang, L., Martin, S. G., Lewis, J. P., & Wilson, J. G. (1998) · Clinical Immunology and Immunopathology · doi:10.1006/clin.1998.4529 · Cited by 68 · see citing works
Dose dependent effect of APOE ε4 on behavioral symptoms in frontal lobe dementia
Engelborghs, S., Dermaut, B., Mariën, P., Symons, A., Vloeberghs, E., Maertens, K., Somers, N., Goeman, J., Rademakers, R., den Broeck, M. V., et al. (2006) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2005.02.005 · Cited by 64 · see citing works
Self-citationWong, W. W., & Farrell, S. A. (1991) · The Journal of Immunology · doi:10.4049/jimmunol.146.2.656 · Cited by 46 · see citing works
Bettens, K., Brouwers, N., Miegroet, H. V., Gil, A., Engelborghs, S., Deyn, P. P. D., Vandenberghe, R. R., Broeckhoven, C. V., & Sleegers, K. (2010) · Journal of Alzheimer s Disease · doi:10.3233/jad-2010-1310 · Cited by 34 · see citing works
Self-citationKumps, C., Roy, N. V., Heyrman, L., Goossens, D., Del‐Favero, J., Noguera, R., Vandesompele, J., Speleman, F., & Preter, K. D. (2010) · BMC Genomics · doi:10.1186/1471-2164-11-298 · Cited by 34 · see citing works
González, J. R., Subirana, I., Escaramís, G., Peraza, S., Cáceres, A., Estivill, X., & Armengol, L. (2009) · BMC Bioinformatics · doi:10.1186/1471-2105-10-172 · Cited by 24 · see citing works
McLure, C. A., Dawkins, R. L., Williamson, J. F., Davies, R. A., Berry, J. A., Laird, N. L.-J. R., & Gaudieri, S. (2004) · Journal of Molecular Evolution · doi:10.1007/s00239-004-2609-8 · Cited by 12 · see citing works
Flagged first, then by citations
1 of the 39 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
Meta-Analysis of 74,046 Individuals Identifies 11 New Susceptibility Loci for Alzheimer’s Disease
(EADI), E. A. D. I., Lambert, J.-C., (GERAD), G. A. E. R. I. A. D., Alzheimer's Disease Genetic Consortium (ADGC), (CHARGE), C. F. H. A. A. R. I. G. E., Ibrahim-Verbaas, C. A., Harold, D., Naj, A. C., Sims, R., Bellenguez, C., et al. (2013) · Nature Genetics · doi:10.1038/ng.2802 · Cited by 4,336 · see citing works
Self-citationAlzheimer Disease Genetics Consortium (ADGC), Kunkle, B. W., The European Alzheimer’s Disease Initiative (EADI), Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium (CHARGE), Genetic and Environmental Risk in AD/Defining Genetic, P. A. E. R. F. A. D. C. (., Grenier-Boley, B., Sims, R., Bis, J. C., Damotte, V., Naj, A. C., et al. (2019) · Nature Genetics · doi:10.1038/s41588-019-0358-2 · Cited by 2,946 · see citing works
Self-citationDominy, S. S., Lynch, C., Ermini, F., Benedyk, M., Marczyk, A., Konradi, A., Nguyen, M., Haditsch, U., Raha, D., Griffin, C., et al. (2019) · Science Advances · doi:10.1126/sciadv.aau3333 · Cited by 1,966 · see citing works
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
Genetic architectures of psychiatric disorders: the emerging picture and its implications
Sullivan, P. F., Daly, M. J., & O'Donovan, M. (2012) · Nature Reviews Genetics · doi:10.1038/nrg3240 · Cited by 1,177 · see citing works
The genetic landscape of Alzheimer disease: clinical implications and perspectives
Van Cauwenberghe, C., Van Broeckhoven, C., & Sleegers, K. (2016) · Genetics in Medicine · doi:10.1038/gim.2015.117 · Cited by 863 · see citing works
Self-citationIl10 Deficiency Rebalances Innate Immunity to Mitigate Alzheimer-Like Pathology
Guillot-Sestier, M.-V., Doty, K. R., Gate, D., Rodriguez, J., Leung, B. P., Rezai-Zadeh, K., & Town, T. (2015) · Neuron · doi:10.1016/j.neuron.2014.12.068 · Cited by 363 · see citing works
Doens, D., & Fernández, P. L. (2014) · Journal of Neuroinflammation · doi:10.1186/1742-2094-11-48 · Cited by 348 · see citing works
Genetic insights in Alzheimer's disease
Bettens, K., Sleegers, K., & Broeckhoven, C. V. (2012) · The Lancet Neurology · doi:10.1016/s1474-4422(12)70259-4 · Cited by 326 · see citing works
Self-citationGenes associated with Alzheimer&#39;s disease: an overview and current status
Giri, M., Lü, Y., & Zhang, M. (2016) · Clinical Interventions in Aging · doi:10.2147/cia.s105769 · Cited by 311 · 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
Self-citationMicroglial genes regulating neuroinflammation in the progression of Alzheimer's disease
Villegas-Llerena, C., Phillips, A., Garcia-Reitboeck, P., Hardy, J., & Pocock, J. M. (2016) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2015.10.004 · Cited by 270 · 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
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
Ebbert, M., Jensen, T. D., Jansen‐West, K. R., Sens, J. P., Reddy, J. S., Ridge, P. G., Kauwe, J. S. K., Belzil, V., Pregent, L., Carrasquillo, M. M., et al. (2019) · Genome biology · doi:10.1186/s13059-019-1707-2 · Cited by 192 · see citing works
Genetic analysis of quantitative phenotypes in AD and MCI: imaging, cognition and biomarkers
Initiative, A. D. N., Shen, L., Thompson, P. M., Potkin, S. G., Bertram, L., Farrer, L. A., Foroud, T., Green, R. C., Hu, X., Huentelman, M. J., et al. (2013) · Brain Imaging and Behavior · doi:10.1007/s11682-013-9262-z · Cited by 174 · see citing works
Tai, L. M., Ghura, S., Koster, K. P., Liakaite, V., Maienschein‐Cline, M., Kanabar, P., Collins, N., Ben‐Aissa, M., Lei, A. Z., Bahroos, N., et al. (2015) · Journal of Neurochemistry · doi:10.1111/jnc.13072 · Cited by 165 · 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
Late-Onset Alzheimer’s Disease Genes and the Potentially Implicated Pathways
Rosenthal, S. L., & Kamboh, M. I. (2014) · Current Genetic Medicine Reports · doi:10.1007/s40142-014-0034-x · Cited by 153 · see citing works
An evaluation of copy number variation detection tools for cancer using whole exome sequencing data
Zare, F., Dow, M. T., Monteleone, N. J., Hosny, A., & Nabavi, S. (2017) · BMC Bioinformatics · doi:10.1186/s12859-017-1705-x · Cited by 147 · see citing works
Physiological and metabolic approach of plastic additive effects: Immune cells responses
Burgos-Aceves, M. A., Abo‐Al‐Ela, H. G., & Faggio, C. (2020) · Journal of Hazardous Materials · doi:10.1016/j.jhazmat.2020.124114 · Cited by 146 · see citing works
Microglial Malfunction: The Third Rail in the Development of Alzheimer's Disease
Mhatre, S. D., Tsai, C. A., Rubin, A. J., James, M. L., & Andreasson, K. I. (2015) · Trends in Neurosciences · doi:10.1016/j.tins.2015.08.006 · Cited by 134 · see citing works
Complement receptor 1 (CR1) and Alzheimer's disease
Crehan, H., Holton, P., Wray, S., Pocock, J., Guerreiro, R., & Hardy, J. (2012) · Immunobiology · doi:10.1016/j.imbio.2011.07.017 · Cited by 129 · see citing works
Genetic architecture of Alzheimer's disease
Neuner, S. M., TCW, J., & Goate, A. M. (2020) · Neurobiology of Disease · doi:10.1016/j.nbd.2020.104976 · Cited by 126 · see citing works
“CNVs have also been identified as modifying risk for LOAD; a functional CNV in the gene CR1 modifying isoform production was shown to increase risk for LOAD in two populations (Brouwers et al., 2012), among others (Swaminathan et al.”
BackgroundPotential Bidirectional Relationship Between Periodontitis and Alzheimer’s Disease
Liccardo, D., Marzano, F., Carraturo, F., Guida, M., Femminella, G. D., Bencivenga, L., Agrimi, J., Addonizio, A., Melino, I., Valletta, A., et al. (2020) · Frontiers in Physiology · doi:10.3389/fphys.2020.00683 · Cited by 137 · see citing works
Linnartz‐Gerlach, B., & Neumann, H. (2012) · Glia · doi:10.1002/glia.22359 · Cited by 117 · see citing works
Stilling, R. M., Benito, E., Barth, J., Gertig, M., Capece, V., Burckhardt, S., Bonn, S., & Fischer, A. (2014) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2014.00373 · Cited by 116 · see citing works
Xue, X., Wu, J., Ricklin, D., Forneris, F., Crescenzio, P. D., Schmidt, C. Q., Granneman, J. C. M., Sharp, T. H., Lambris, J. D., & Gros, P. (2017) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.3427 · Cited by 116 · see citing works
The therapeutics of Alzheimer's disease: Where we stand and where we are heading
Selkoe, D. J. (2013) · Annals of Neurology · doi:10.1002/ana.24001 · Cited by 112 · see citing works
The Genetics of Alzheimer’s Disease
Barber, R. C. (2012) · Scientifica · doi:10.6064/2012/246210 · Cited by 111 · see citing works
New tricks for an ancient system: Physiological and pathological roles of complement in the CNS
Tenner, A. J., Stevens, B., & Woodruff, T. M. (2018) · Molecular Immunology · doi:10.1016/j.molimm.2018.06.264 · Cited by 112 · see citing works
Western, D., Timsina, J., Wang, L., Wang, C., Yang, C., Phillips, B., Wang, Y., Liu, M., Ali, M., Beric, A., et al. (2024) · Nature Genetics · doi:10.1038/s41588-024-01972-8 · Cited by 111 · see citing works
Sleegers, K., Bettens, K., De Roeck, A., Van Cauwenberghe, C., Cuyvers, E., Verheijen, J., Struyfs, H., Van Dongen, J., Vermeulen, S., Engelborghs, S., et al. (2015) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2015.02.013 · Cited by 106 · see citing works
Self-citationWes, P. D., Easton, A. E., Corradi, J., Barten, D. M., Devidze, N., DeCarr, L. B., Truong, A. B., He, A., Barrezueta, N. X., Polson, C. T., et al. (2014) · PLoS ONE · doi:10.1371/journal.pone.0106050 · Cited by 105 · see citing works
López González, I., Garcia-Esparcia, P., Llorens, F., & Ferrer, I. (2016) · International Journal of Molecular Sciences · doi:10.3390/ijms17020206 · Cited by 101 · see citing works
Keene, C. D., Cudaback, E., Li, X., Montine, K. S., & Montine, T. J. (2011) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2011.08.002 · Cited by 103 · see citing works
Wang, M., Song, W., Chen, M., Wang, Q., Zhou, X., Xu, P., Krek, A., Yoon, Y., Ho, L., Orr, M. E., et al. (2022) · Molecular Neurodegeneration · doi:10.1186/s13024-022-00517-z · Cited by 100 · see citing works
Blockage of CR1 prevents activation of rodent microglia
Crehan, H., Hardy, J., & Pocock, J. (2013) · Neurobiology of Disease · doi:10.1016/j.nbd.2013.02.003 · Cited by 98 · see citing works
17q21.31 duplication causes prominent tau-related dementia with increased MAPT expression
Guennec, K. L., Quenez, O., Nicolas, G., Wallon, D., Rousseau, S., Richard, A.-C., Alexander, J., Paschou, P., Charbonnier, C., Bellenguez, C., et al. (2016) · Molecular Psychiatry · doi:10.1038/mp.2016.226 · Cited by 96 · see citing works
Self-citationGenomics of Alzheimer’s disease implicates the innate and adaptive immune systems
Li, Y., Laws, S. M., Miles, L. A., Wiley, J. S., Huang, X., Masters, C. L., & Gu, B. J. (2021) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-021-03986-5 · Cited by 93 · see citing works
EFAD transgenic mice as a human APOE relevant preclinical model of Alzheimerʼns disease
Tai, L. M., Balu, D., Avila-Munoz, E., Abdullah, L., Thomas, R., Collins, N., Valencia-Olvera, A. C., & LaDu, M. J. (2017) · Journal of Lipid Research · doi:10.1194/jlr.r076315 · Cited by 93 · see citing works
Effect of Complement CR1 on Brain Amyloid Burden During Aging and Its Modification by APOE Genotype
Thambisetty, M., An, Y., Nalls, M., Sojkova, J., Swaminathan, S., Zhou, Y., Singleton, A. B., Wong, D. F., Ferrucci, L., Saykin, A. J., et al. (2013) · Biological Psychiatry · doi:10.1016/j.biopsych.2012.08.015 · Cited by 90 · see citing works
A coding variant in CR1 interacts with APOE-ɛ4 to influence cognitive decline
Keenan, B. T., Shulman, J. M., Chibnik, L. B., Raj, T., Tran, D., Sabuncu, M. R., Initiative, T. A. D. N., Allen, A. N., Corneveaux, J. J., Hardy, J., et al. (2012) · Human Molecular Genetics · doi:10.1093/hmg/dds054 · Cited by 93 · see citing works
Fonseca, M. I., Chu, S., Pierce, A. L., Brubaker, W. D., Hauhart, R. E., Mastroeni, D., Clarke, E. V., Rogers, J., Atkinson, J. P., & Tenner, A. J. (2016) · PLOS ONE · doi:10.1371/journal.pone.0149792 · Cited by 87 · see citing works
Zhu, X., Yu, J., Jiang, T., Wang, P., Cao, L., & Tan, L. (2014) · Molecular Neurobiology · doi:10.1007/s12035-014-8723-8 · Cited by 84 · see citing works
Genetic association of CR1 with Alzheimer's disease: A tentative disease mechanism
Hazrati, L., Cauwenberghe, C. V., Brooks, P. L., Brouwers, N., Ghani, M., Sato, C., Cruts, M., Sleegers, K., George‐Hyslop, P. S., Broeckhoven, C. V., et al. (2012) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2012.07.001 · Cited by 82 · see citing works
Self-citationAnalysis of Copy Number Variation in Alzheimer’s Disease: The NIALOAD/ NCRAD Family Study
Swaminathan, S., Shen, L., Kim, S., Inlow, M. H., West, J. D., Faber, K. M., Foroud, T., Mayeux, R. P., & Saykin, A. J. (2012) · Current Alzheimer Research · doi:10.2174/156720512802455331 · 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
Qi, X.-M., & Ma, J. (2017) · Translational Neurodegeneration · doi:10.1186/s40035-017-0091-7 · Cited by 80 · see citing works
An overview of the genes and biomarkers in Alzheimer’s disease
Krishnamurthy, H. K., Jayaraman, V., Krishna, K., Wang, T., Bei, K., Changalath, C., & Rajasekaran, J. J. (2024) · Ageing Research Reviews · doi:10.1016/j.arr.2024.102599 · Cited by 85 · see citing works
Salyakina, D., Cukier, H. N., Lee, J. M., Sacharow, S., Nations, L. D., Ma, D., Jaworski, J. M., Konidari, I., Whitehead, P. L., Wright, H. H., et al. (2011) · PLoS ONE · doi:10.1371/journal.pone.0026049 · Cited by 80 · see citing works
Swaminathan, S., Huentelman, M. J., Corneveaux, J. J., Myers, A., Faber, K. M., Foroud, T., Mayeux, R. P., Shen, L., Kim, S., Turk, M., et al. (2012) · PLoS ONE · doi:10.1371/journal.pone.0050640 · Cited by 79 · see citing works
The Links between Cardiovascular Diseases and Alzheimer's Disease
Leszek, J., Вячеславовна, М. Е., Belousov, D. M., Koutsouraki, E., Szczechowiak, K., Kobusiak−Prokopowicz, M., Mysiak, A., Diniz, B. S., Somasundaram, S. G., Kirkland, C. E., et al. (2020) · Current Neuropharmacology · doi:10.2174/1570159x18666200729093724 · Cited by 84 · see citing works
Genetic Markers of Alzheimer’s Disease
Perković, M. N., & Pivac, N. (2019) · Advances in experimental medicine and biology · doi:10.1007/978-981-32-9721-0_3 · Cited by 75 · see citing works
Transcriptomics in Alzheimer’s Disease: Aspects and Challenges
Bagyinszky, E., Giau, V. V., & An, S. A. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21103517 · Cited by 75 · see citing works
Dai, Y., Huo, X., Zhang, Y., Yang, T., Li, M., & Xu, X. (2017) · The Science of The Total Environment · doi:10.1016/j.scitotenv.2017.03.080 · Cited by 74 · see citing works
Late-onset Alzheimer disease risk variants mark brain regulatory loci
Allen, M., Kachadoorian, M., Carrasquillo, M. M., Karhade, A., Manly, L., Burgess, J. D., Wang, C., Serie, D., Wang, X., Siuda, J., et al. (2015) · Neurology Genetics · doi:10.1212/nxg.0000000000000012 · Cited by 73 · see citing works
Targeting Microglia in Alzheimer’s Disease: Pathogenesis and Potential Therapeutic Strategies
Sun, Z., Zhang, X., So, K.-F., Jiang, W., & Chiu, K. (2024) · Biomolecules · doi:10.3390/biom14070833 · Cited by 71 · see citing works
Complement activation as a biomarker for Alzheimer's disease
Aiyaz, M., Lupton, M. K., Proitsi, P., Powell, J. F., & Lovestone, S. (2011) · Immunobiology · doi:10.1016/j.imbio.2011.07.023 · Cited by 69 · see citing works
Sweet, R. A., Seltman, H. J., Emanuel, J. E., López, O. L., Becker, J. T., Bis, J. C., Weamer, E. A., DeMichele‐Sweet, M. A. A., & Kuller, L. H. (2012) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2012.11121815 · Cited by 66 · see citing works
Evaluation of late-onset Alzheimer disease genetic susceptibility risks in a Canadian population
Omoumi, A., Fok, A., Greenwood, T., Sadovnick, A. D., Feldman, H., & Hsiung, G. R. (2013) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2013.09.025 · Cited by 64 · see citing works
Insights into the Potential Role of Mercury in Alzheimer’s Disease
Bjørklund, G., Tinkov, A. A., Dadar, M., Rahman, M. M., Chirumbolo, S., Skalny, A. V., Геннадиевна, С. М., Haley, B. E., Ajsuvakova, O. P., & Aaseth, J. (2019) · Journal of Molecular Neuroscience · doi:10.1007/s12031-019-01274-3 · Cited by 64 · see citing works
Targeting Microglia-Synapse Interactions in Alzheimer’s Disease
Piccioni, G., Mango, D., Saidi, A., Corbo, M., & Nisticò, R. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22052342 · Cited by 62 · see citing works
Ghani, M., Pinto, D., Lee, J. H., Grinberg, Y., Sato, C., Moreno, D., Scherer, S. W., Mayeux, R. P., George‐Hyslop, P. S., & Rogaeva, E. A. (2012) · G3 Genes Genomes Genetics · doi:10.1534/g3.111.000869 · Cited by 63 · see citing works
The Role of the Microbiota–Gut–Brain Axis and Antibiotics in ALS and Neurodegenerative Diseases
Obrenovich, M., Jaworski, H., Tadimalla, T., Mistry, A., Sykes, L., Perry, G., & Bonomo, R. (2020) · Microorganisms · doi:10.3390/microorganisms8050784 · Cited by 62 · see citing works
Alzheimer's loci: epigenetic associations and interaction with genetic factors
Chibnik, L. B., Yu, L., Eaton, M. L., Srivastava, G., Schneider, J. A., Kellis, M., Bennett, D. A., & De Jager, P. L. (2015) · Annals of Clinical and Translational Neurology · doi:10.1002/acn3.201 · Cited by 60 · see citing works
Large multi-ethnic genetic analyses of amyloid imaging identify new genes for Alzheimer disease
Ali, M., Archer, D. B., Gorijala, P., Western, D., Timsina, J., Fernández, M. V., Wang, T., Satizábal, C. L., Yang, Q., Beiser, A., et al. (2023) · Acta Neuropathologica Communications · doi:10.1186/s40478-023-01563-4 · Cited by 59 · see citing works
snpXplorer: a web application to explore human SNP-associations and annotate SNP-sets
Tesi, N., van der Lee, S. J., Hulsman, M., Holstege, H. H., & Reinders, M. J. T. (2021) · Nucleic Acids Research · doi:10.1093/nar/gkab410 · Cited by 49 · see citing works
Copy Number Variants in Alzheimer’s Disease
Cuccaro, D., Marco, E. V. D., Cittadella, R., & Cavallaro, S. (2016) · Journal of Alzheimer s Disease · doi:10.3233/jad-160469 · Cited by 49 · see citing works
Initial Assessment of the Pathogenic Mechanisms of the Recently Identified Alzheimer Risk Loci
Holton, P., Ryten, M., Nalls, M., Trabzuni, D., Weale, M. E., Hernandez, D., Crehan, H., Gibbs, J. R., Mayeux, R., Haines, J. L., et al. (2013) · Annals of Human Genetics · doi:10.1111/ahg.12000 · Cited by 48 · see citing works
Implication of common and disease specific variants in CLU, CR1, and PICALM
Ferrari, R., Moreno, J. H., Minhajuddin, A., O’Bryant, S. E., Reisch, J., Barber, R. C., & Momeni, P. (2012) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2012.01.110 · Cited by 47 · see citing works
The plasma peptides of Alzheimer’s disease
Florentinus-Mefailoski, A., Bowden, P., Scheltens, P., Killestein, J., Teunissen, C. E., & Marshall, J. G. (2021) · Clinical Proteomics · doi:10.1186/s12014-021-09320-2 · Cited by 46 · see citing works
Humphries, C., Kohli, M. A., Whitehead, P. L., Mash, D. C., Pericak‐Vance, M. A., & Gilbert, J. R. (2015) · Molecular and Cellular Neuroscience · doi:10.1016/j.mcn.2015.05.003 · Cited by 47 · see citing works
Harnessing Immunoproteostasis to Treat Neurodegenerative Disorders
Golde, T. E. (2019) · Neuron · doi:10.1016/j.neuron.2019.02.027 · Cited by 45 · see citing works
Genetic risk factors for Alzheimer disease: emerging roles of microglia in disease pathomechanisms
Takatori, S., Wang, W., Iguchi, A., & Tomita, T. (2019) · Advances in Experimental Medicine and Biology · doi:10.1007/978-3-030-05542-4_5 · Cited by 44 · see citing works
Regulation of microglial survival and proliferation in health and diseases
Ulland, T. K., Wang, Y., & Colonna, M. (2015) · Seminars in Immunology · doi:10.1016/j.smim.2016.03.011 · Cited by 43 · see citing works
Kretzschmar, G. C., Bumiller‐Bini, V., Filho, M. A. G., Zonta, Y. R., Yu, K. S. T., de Souza, R. L. R., Dias‐Melicio, L. A., & Boldt, A. B. W. (2021) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2021.630869 · Cited by 42 · 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
Afsar, A., Castro, M. D. C. C., Soladogun, A. S., & Li, Z. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24087258 · Cited by 42 · see citing works
Firdaus, Z., & Li, X. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25042320 · Cited by 43 · see citing works
Alzheimer's disease is associated with low density of the long CR1 isoform
Mahmoudi, R., Kisserli, A., Novella, J., Donvito, B., Dramé, M., Réveil, B., Duret, V., Jolly, D., Pham, B., & Cohen, J. H. M. (2015) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2015.01.006 · Cited by 39 · see citing works
Hong, D., Zhang, C., Wu, W., Lu, X., & Zhang, L. (2023) · Frontiers in Neurology · doi:10.3389/fneur.2023.1133546 · Cited by 38 · see citing works
Arefin, A. S., Mathieson, L., Johnstone, D. M., Berretta, R. E., & Moscato, P. (2012) · PLoS ONE · doi:10.1371/journal.pone.0045535 · Cited by 39 · see citing works
Morello, G., Guarnaccia, M., Spampinato, A. G., Salomone, S., D’Agata, V., Conforti, F. L., Aronica, E., & Cavallaro, S. (2019) · Scientific Reports · doi:10.1038/s41598-019-46355-w · Cited by 38 · see citing works
New genetic players in late-onset Alzheimer's disease
Misra, A., Chakrabarti, S. S., & Gambhir, I. S. (2018) · The Indian Journal of Medical Research · doi:10.4103/ijmr.ijmr_473_17 · Cited by 36 · see citing works
Kunkle, B., Grenier-Boley, B., Sims, R., Bis, J., Naj, A., Boland, A., Vronskaya, M., van der Lee, S., Amlie-Wolf, A., Bellenguez, C., et al. (2018) · doi:10.1101/294629 · Cited by 35 · see citing works
Self-citationLinnartz‐Gerlach, B., Schuy, C., Shahraz, A., Tenner, A. J., & Neumann, H. (2015) · Glia · doi:10.1002/glia.22901 · Cited by 34 · see citing works
Coherent Somatic Mutation in Autoimmune Disease
Ross, K. A. (2014) · PLoS ONE · doi:10.1371/journal.pone.0101093 · Cited by 34 · see citing works
Complement receptor 1 gene (CR1) intragenic duplication and risk of Alzheimer’s disease
ARUK Consortium, Kucukkilic, E., Brookes, K., Barber, I., Guetta-Baranes, T., Morgan, K., & Hollox, E. J. (2018) · Human Genetics · doi:10.1007/s00439-018-1883-2 · Cited by 33 · see citing works
Targeting Infectious Agents as a Therapeutic Strategy in Alzheimer’s Disease
Fülöp, T., Munawara, U., Larbi, A., Desroches, M., Rodrigues, S., Catanzaro, M., Guidolin, A., Khalil, A., Bernier, F., Barron, A. E., et al. (2020) · CNS Drugs · doi:10.1007/s40263-020-00737-1 · Cited by 32 · see citing works
Chapman, J., Rees, E., Harold, D. H., Ivanov, D. K., Gerrish, A., Sims, R., Hollingworth, P., Stretton, A., Holmans, P., Owen, M. J., et al. (2012) · Human Molecular Genetics · doi:10.1093/hmg/dds476 · Cited by 32 · see citing works
Genome-Wide Scan for Copy Number Variation Association with Age at Onset of Alzheimer's Disease
Szigeti, K., Lal, D., Li, Y., Doody, R. S., Wilhelmsen, K. C., Li, Y., Liu, S., & Ma, C. (2012) · Journal of Alzheimer s Disease · doi:10.3233/jad-2012-121285 · Cited by 31 · see citing works
Relationship Between Genetic Risk Factors and Markers for Alzheimer’s Disease Pathology
Elias-Sonnenschein, L. S., Bertram, L., & Visser, P. J. (2012) · Biomarkers in Medicine · doi:10.2217/bmm.12.56 · Cited by 28 · see citing works
The Impact of Complement Genes on the Risk of Late-Onset Alzheimer’s Disease
Carpanini, S. M., Harwood, J. C., Baker, E. A., Torvell, M., Sims, R., Williams, J. H., & Morgan, B. P. (2021) · Genes · doi:10.3390/genes12030443 · Cited by 28 · see citing works
Kõks, S., Overall, R. W., Ivask, M., Soomets, U., Guha, M., Vasar, E., Fernandes, C., & Schalkwyk, L. C. (2013) · Physiological Genomics · doi:10.1152/physiolgenomics.00122.2012 · Cited by 28 · see citing works
Copy Number Variants in miR-138 as a Potential Risk Factor for Early-Onset Alzheimer’s Disease
Boscher, E., Husson, T., Quenez, O., Laquerrière, A., Marguet, F., Cassinari, K., Wallon, D., Martinaud, O., Charbonnier, C., Nicolas, G., et al. (2019) · Journal of Alzheimer s Disease · doi:10.3233/jad-180940 · Cited by 27 · see citing works
Genetic Insights into the Impact of Complement in Alzheimer’s Disease
Torvell, M., Carpanini, S. M., Daskoulidou, N., Byrne, R. A. J., Sims, R., & Morgan, B. P. (2021) · Genes · doi:10.3390/genes12121990 · Cited by 27 · see citing works
Mahmoudi, R., Feldman, S. F., Kisserli, A., Duret, V., Tabary, T., Bertholon, L.-A., Badr, S., Nonnonhou, V., Cesar, A., Neuraz, A., et al. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19082175 · Cited by 26 · see citing works
Initiative, A. D. N., Zhu, X., Wang, H.-F., Jiang, T., Lu, H., Tan, M., Tan, C., Tan, L., Tan, L., & Yu, J. (2016) · Molecular Neurobiology · doi:10.1007/s12035-015-9638-8 · Cited by 26 · see citing works
- Authors
- Brouwers, N., Van Cauwenberghe, C., Engelborghs, S., Lambert, J.-C., Bettens, K., Le Bastard, N., Pasquier, F., Montoya, A. G., Peeters, K., Mattheijssens, M., Vandenberghe, R., De Deyn, P. P., Cruts, M., Amouyel, P., Sleegers, K., & Van Broeckhoven, C.
- Affiliations
- VIB-UAntwerp Center for Molecular Neurology (BE)
- University of Antwerp (BE)
- Inserm (FR)
- Centre Hospitalier Universitaire de Lille (FR)
- KU Leuven (BE)
- Venue
- Molecular Psychiatry
- Published
- 2011-03-15
- Volume
- 17
- Issue
- 2
- Pages
- 223-233
- ISSN
- 1359-4184 (ISSN-L)
- 1476-5578
- PMC
- PMC3265835
- OpenAlex
- W2153240577
- Cited by
- 227
- References
- 39
- Citations by year
- 2026: 8 · 2025: 11 · 2024: 17 · 2023: 13 · 2022: 9 · 2021: 23 · 2020: 15 · 2019: 16 · 2018: 9 · 2017: 11 · 2016: 13 · 2015: 20 · 2014: 13 · 2013: 16 · 2012: 27
- FWCI
- 13.52
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by-nc-nd
- www.springer.com/tdm (unspecified)
- Locations
- Molecular Psychiatry (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- HAL (submittedVersion, other-oa)
- Trinity's Access to Research Output (TARA) (Trinity College Dublin) (submittedVersion)
- VUBIR (Vrije Universiteit Brussel) (submittedVersion)
- Funders
- Institut National de la Santé et de la Recherche Médicale
- Belgian Federal Science Policy Office
- Fonds Wetenschappelijk Onderzoek (P6/43)
- Universiteit Antwerpen
- Vlaamse regering
- Instituut Born-Bunge
- Bijzonder Onderzoeksfonds UGent
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Immunology and Microbiology › Immunology › Complement system in diseases
- Keywords
- Alzheimer's disease, complement receptor 1, copy number variation, complement system, APOE ε4, amyloid-beta, cerebrospinal fluid biomarkers, risk haplotype, genetic risk
- MeSH terms
- Aged, Aged, 80 and over, Alzheimer Disease, Female, Gene Frequency, Genotype, Humans, Male, Peptide Fragments, Receptors, Complement, Meta-Analysis as Topic, Cohort Studies, Logistic Models, Odds Ratio, Amyloid beta-Peptides, tau Proteins, Complement Factor I, Polymorphism, Single Nucleotide, Apolipoprotein E4, Genome-Wide Association Study, DNA Copy Number Variations, Segmental Duplications, Genomic
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
