Deleterious ABCA7 mutations and transcript rescue mechanisms in early onset Alzheimer’s disease
Open accessAbstract
Premature termination codon (PTC) mutations in the ATP-Binding Cassette, Sub-Family A, Member 7 gene (ABCA7) have recently been identified as intermediate-to-high penetrant risk factor for late-onset Alzheimer's disease (LOAD). High variability, however, is observed in downstream ABCA7 mRNA and protein expression, disease penetrance, and onset age, indicative of unknown modifying factors. Here, we investigated the prevalence and disease penetrance of ABCA7 PTC mutations in a large early onset AD (EOAD)-control cohort, and examined the effect on transcript level with comprehensive third-generation long-read sequencing. We characterized the ABCA7 coding sequence with next-generation sequencing in 928 EOAD patients and 980 matched control individuals. With MetaSKAT rare variant association analysis, we observed a fivefold enrichment (p = 0.0004) of PTC mutations in EOAD patients (3%) versus controls (0.6%). Ten novel PTC mutations were only observed in patients, and PTC mutation carriers in general had an increased familial AD load. In addition, we observed nominal risk reducing trends for three common coding variants. Seven PTC mutations were further analyzed using targeted long-read cDNA sequencing on an Oxford Nanopore MinION platform. PTC-containing transcripts for each investigated PTC mutation were observed at varying proportion (5-41% of the total read count), implying incomplete nonsense-mediated mRNA decay (NMD). Furthermore, we distinguished and phased several previously unknown alternative splicing events (up to 30% of transcripts). In conjunction with PTC mutations, several of these novel ABCA7 isoforms have the potential to rescue deleterious PTC effects. In conclusion, ABCA7 PTC mutations play a substantial role in EOAD, warranting genetic screening of ABCA7 in genetically unexplained patients. Long-read cDNA sequencing revealed both varying degrees of NMD and transcript-modifying events, which may influence ABCA7 dosage, disease severity, and may create opportunities for therapeutic interventions in AD.
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?
For the 24 signals reported, other evidence indicates that APOE, ABCA7, BIN1, TREM2, SORL1, ADAM10, SPI1, and CR1 are the true Alzheimer's disease risk genes.
“For the 24 signals reported here, other evidence indicates that APOE35,36, ABCA7 (refs. 37–40), BIN1 (ref. 41), TREM2 (refs. 7,8), SORL1 (refs. 42,43), ADAM10 (ref. 44), SPI1 (ref. 45), and CR1 (ref. 46) are the true Alzheimer’s disease risk gene”
From Genetic meta-analysis of diagnosed Alzheimer’s disease identifies new risk loci and implicates Aβ, tau, immunity and lipid processing (2019) · cites this paper as [40]
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
Trimmomatic: a flexible trimmer for Illumina sequence data
Bolger, A. M., Lohse, M., & Usadel, B. (2014) · Bioinformatics · doi:10.1093/bioinformatics/btu170 · Cited by 65,548 · see citing works
Fast and accurate short read alignment with Burrows-Wheeler transform
Li, H., & Durbin, R. (2009) · Bioinformatics · doi:10.1093/bioinformatics/btp324 · Cited by 58,607 · see citing works
PLINK: a tool set for whole-genome association and population-based linkage analyses.
Purcell, S., Neale, B., Todd-Brown, K., Thomas, L., Ferreira, M. A. R., Bender, D., Maller, J., Sklar, P., de Bakker, P. I. W., Daly, M. J., et al. (2007) · The American Journal of Human Genetics · doi:10.1086/519795 · Cited by 34,089 · see citing works
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
McKhann, G. M., Knopman, D. S., Chertkow, H., Hyman, B. T., Jack, C. R., Kawas, C. H., Klunk, W. E., Koroshetz, W. J., Manly, J. J., Mayeux, R., et al. (2011) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2011.03.005 · Cited by 18,657 · see citing works
Kim, D., Pertea, G., Trapnell, C., Pimentel, H., Kelley, R., & Salzberg, S. L. (2013) · Genome Biology · doi:10.1186/gb-2013-14-4-r36 · Cited by 12,668 · see citing works
Fast and accurate long-read alignment with Burrows-Wheeler transform.
Li, H., & Durbin, R. (2010) · Bioinformatics · doi:10.1093/bioinformatics/btp698 · Cited by 12,063 · see citing works
Cingolani, P., Platts, A., Wang, L. L., Coon, M., Nguyen, T., Wang, L., Land, S. J., Lu, X., & Ruden, D. M. (2012) · Fly · doi:10.4161/fly.19695 · Cited by 11,816 · see citing works
Circos: An information aesthetic for comparative genomicsPreprint
Krzywinski, M. I., Schein, J. E., Birol, İ., Connors, J. M., Gascoyne, R. D., Horsman, D. E., Jones, S. J. M., & Marra, M. A. (2009) · Genome Research · doi:10.1101/gr.092759.109 · Cited by 10,838 · see citing works
A general framework for estimating the relative pathogenicity of human genetic variants
Kircher, M., Witten, D. M., Jain, P., O'Roak, B. J., Cooper, G. M., & Shendure, J. (2014) · Nature Genetics · doi:10.1038/ng.2892 · Cited by 6,183 · see citing works
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-citationHarold, 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-citationHyman, B. T., Phelps, C. H., Beach, T. G., Bigio, E. H., Cairns, N. J., Carrillo, M. C., Dickson, D. W., Duyckaerts, C., Frosch, M. P., Masliah, E., et al. (2012) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2011.10.007 · Cited by 3,092 · see citing works
GMAP: A genomic mapping and alignment program for mRNA and EST sequences
Wu, T. D., & Watanabe, C. K. (2005) · Bioinformatics · doi:10.1093/bioinformatics/bti310 · Cited by 2,354 · 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
Self-citationInitiative, 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
Self-citationNaj, 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
Nyholt, D. R. (2004) · The American Journal of Human Genetics · doi:10.1086/383251 · Cited by 1,699 · see citing works
Genome-wide Analysis of Genetic Loci Associated With Alzheimer Disease
Seshadri, S. (2010) · JAMA · doi:10.1001/jama.2010.574 · Cited by 1,219 · see citing works
The Evolutionary Landscape of Alternative Splicing in Vertebrate Species
Barbosa-Morais, N. L., Irimia, M., Pan, Q., Xiong, H. Y., Gueroussov, S., Lee, L. J., Slobodeniuc, V., Kutter, C., Watt, S., Çolak, R., et al. (2012) · Science · doi:10.1126/science.1230612 · Cited by 1,063 · see citing works
Molecular genetics of early-onset Alzheimer’s disease revisited
Cacace, R., Sleegers, K., & Van Broeckhoven, C. (2016) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2016.01.012 · Cited by 617 · see citing works
Self-citationReitz, 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
Poretools: a toolkit for analyzing nanopore sequence data
Loman, N. J., & Quinlan, A. R. (2014) · Bioinformatics · doi:10.1093/bioinformatics/btu555 · Cited by 376 · see citing works
Loss-of-function variants in ABCA7 confer risk of Alzheimer's disease
DemGene, Steinberg, S., Stefansson, H., Jonsson, T., Johannsdottir, H., Ingason, A., Helgason, H., Sulem, P., Magnusson, O. T., Gudjonsson, S. A., et al. (2015) · Nature Genetics · doi:10.1038/ng.3246 · Cited by 324 · see citing works
novoSNP, a novel computational tool for sequence variation discoveryPreprint
Weckx, S., Del‐Favero, J., Rademakers, R., Claes, L. R. F., Cruts, M., Jonghe, P. D., Broeckhoven, C. V., & Rijk, P. D. (2005) · Genome Research · doi:10.1101/gr.2754005 · Cited by 285 · 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-citationOptimized filtering reduces the error rate in detecting genomic variants by short-read sequencing
Reumers, J., Rijk, P. D., Zhao, H., Liekens, A. M. L., Smeets, D., Cleary, J., Loo, P. V., Bossche, M. J. A. V. D., Catthoor, K., Sabbe, B., et al. (2011) · Nature Biotechnology · doi:10.1038/nbt.2053 · Cited by 234 · see citing works
Jehle, A. W., Gardai, S. J., Li, S., Linsel‐Nitschke, P., Morimoto, K., Janssen, W. J., Vandivier, R. W., Wang, N., Greenberg, S., Dale, B. M., et al. (2006) · The Journal of Cell Biology · doi:10.1083/jcb.200601030 · Cited by 213 · see citing works
Kim, W. S., Li, H., Ruberu, K. R., Chan, S. L., Elliott, D. A., Low, J. K., Cheng, D., Karl, T., & Garner, B. (2013) · Journal of Neuroscience · doi:10.1523/jneurosci.4165-12.2013 · Cited by 209 · see citing works
Sense from nonsense: therapies for premature stop codon diseases
Bidou, L., Allamand, V., Rousset, J., & Namy, O. (2012) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2012.09.008 · Cited by 196 · see citing works
Novel late-onset Alzheimer disease loci variants associate with brain gene expression
Allen, M., Zou, F., Chai, H. S., Younkin, C. S., Crook, J. E., Pankratz, V. S., Carrasquillo, M. M., Rowley, C. N., Nair, A., Middha, S., et al. (2012) · Neurology · doi:10.1212/wnl.0b013e3182605801 · Cited by 164 · see citing works
Oikonomopoulos, S., Wang, Y. C., Djambazian, H. H. V., Badescu, D., & Ragoussis, J. (2016) · Scientific Reports · doi:10.1038/srep31602 · Cited by 153 · see citing works
Cuyvers, E., De Roeck, A., Van den Bossche, T., Van Cauwenberghe, C., Bettens, K., Vermeulen, S., Mattheijssens, M., Peeters, K., Engelborghs, S., Vandenbulcke, M., et al. (2015) · The Lancet Neurology · doi:10.1016/s1474-4422(15)00133-7 · Cited by 152 · see citing works
Self-citationVardarajan, B. N., Ghani, M., Kahn, A., Sheikh, S., Sato, C., Barral, S., Lee, J. H., Cheng, R., Reitz, C., Lantigua, R., et al. (2015) · Annals of Neurology · doi:10.1002/ana.24466 · Cited by 148 · see citing works
ABCA7 Deficiency Accelerates Amyloid-β Generation and Alzheimer's Neuronal Pathology
Sakae, N., Liu, C., Shinohara, M., Frisch‐Daiello, J. L., Ma, L., Yamazaki, Y., Tachibana, M., Younkin, L. H., Kurti, A., Carrasquillo, M. M., et al. (2016) · Journal of Neuroscience · doi:10.1523/jneurosci.3757-15.2016 · Cited by 146 · see citing works
Comparison of nonsense-mediated mRNA decay efficiency in various murine tissues
Zetoune, A. B., Fontanière, S., Lutringer-Magnin, D., Anczuków, O., Buisson, M., Zhang, C. X., & Mazoyer, S. (2008) · BMC Genetics · doi:10.1186/1471-2156-9-83 · Cited by 136 · see citing works
ATP-binding cassette transporter A7 (ABCA7) loss of function alters Alzheimer amyloid processing
Satoh, K., Abe-Dohmae, S., Yokoyama, S., St George-Hyslop, P., & Fraser, P. E. (2015) · Journal of Biological Chemistry · doi:10.1074/jbc.m115.655076 · Cited by 128 · see citing works
Verheijen, J., Van den Bossche, T., van der Zee, J., Engelborghs, S., Sanchez-Valle, R., Lladó, A., Graff, C., Thonberg, H., Pastor, P., Ortega-Cubero, S., et al. (2016) · Acta Neuropathologica · doi:10.1007/s00401-016-1566-9 · Cited by 112 · see citing works
Self-citationIwamoto, N., Abe-Dohmae, S., Sato, R., & Yokoyama, S. (2006) · Journal of Lipid Research · doi:10.1194/jlr.m600127-jlr200 · Cited by 110 · see citing works
ABCA7 expression is associated with Alzheimer's disease polymorphism and disease status
Vasquez, J. B., Fardo, D. W., & Estus, S. (2013) · Neuroscience Letters · doi:10.1016/j.neulet.2013.09.058 · Cited by 101 · see citing works
<i>ABCA7</i> frameshift deletion associated with Alzheimer disease in African Americans
Cukier, H. N., Kunkle, B. W., Vardarajan, B. N., Rolati, S., Hamilton-Nelson, K. L., Kohli, M. A., Whitehead, P. L., Dombroski, B. A., Van Booven, D., Lang, R., et al. (2016) · Neurology Genetics · doi:10.1212/nxg.0000000000000079 · Cited by 100 · see citing works
ABCA7 Mediates Phagocytic Clearance of Amyloid-β in the Brain
Fu, Y., Hsiao, J.-H. T., Paxinos, G., Halliday, G. M., & Kim, W. S. (2016) · Journal of Alzheimer s Disease · doi:10.3233/jad-160456 · Cited by 98 · see citing works
Splicing therapy for neuromuscular disease
Douglas, A. G. L., & Wood, M. J. A. (2013) · Molecular and Cellular Neuroscience · doi:10.1016/j.mcn.2013.04.005 · Cited by 97 · see citing works
Pitfalls of haplotype phasing from amplicon-based long-read sequencing
Laver, T. W., Caswell, R. C., Moore, K., Poschmann, J., Johnson, M. B., Owens, M., Ellard, S., Paszkiewicz, K. H., & Weedon, M. N. (2016) · Scientific Reports · doi:10.1038/srep21746 · Cited by 79 · see citing works
Potential role of ABCA7 in cellular lipid efflux to apoA-I
Linsel‐Nitschke, P., Jehle, A. W., Shan, J., Cao, G., Bacic, D., Lan, D., Wang, N., & Tall, A. R. (2004) · Journal of Lipid Research · doi:10.1194/jlr.m400247-jlr200 · Cited by 74 · see citing works
Roles of ATP-Binding Cassette Transporter A7 in Cholesterol Homeostasis and Host Defense System
Tanaka, N., Abe-Dohmae, S., Iwamoto, N., & Yokoyama, S. (2011) · Journal of Atherosclerosis and Thrombosis · doi:10.5551/jat.6726 · Cited by 73 · see citing works
<i>ABCA7</i> rare variants and Alzheimer disease risk
Le Guennec, K., Nicolas, G., Quenez, O., Charbonnier, C., Wallon, D., Bellenguez, C., Grenier-Boley, B., Rousseau, S., Richard, A.-C., Rovelet-Lecrux, A., et al. (2016) · Neurology · doi:10.1212/wnl.0000000000002627 · Cited by 69 · see citing works
ABCA7 p.G215S as potential protective factor for Alzheimer's disease
Sassi, C., Nalls, M. A., Ridge, P. G., Gibbs, J. R., Ding, J., Lupton, M. K., Troakes, C., Lunnon, K., Al‐Sarraj, S., Brown, K. S., et al. (2016) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2016.04.004 · Cited by 55 · see citing works
Self-citationUnderstanding the function of ABCA7 in Alzheimer's disease
Li, H., Karl, T., & Garner, B. (2015) · Biochemical Society Transactions · doi:10.1042/bst20150105 · Cited by 50 · see citing works
ABCA7 loss-of-function variants, expression, and neurologic disease risk
Allen, M., Lincoln, S., Corda, M., Watzlawik, J. O., Carrasquillo, M. M., Reddy, J. S., Burgess, J. D., Nguyen, T., Malphrus, K. G., Petersen, R. C., et al. (2017) · Neurology Genetics · doi:10.1212/nxg.0000000000000126 · Cited by 37 · see citing works
Phenotypic characteristics of Alzheimer patients carrying an ABCA7 mutation
den Bossche, T. V., Sleegers, K., Cuyvers, E., Engelborghs, S., Sieben, A., Roeck, A. D., Cauwenberghe, C. V., Vermeulen, S., den Broeck, M. V., Laureys, A., et al. (2016) · Neurology · doi:10.1212/wnl.0000000000002628 · Cited by 33 · see citing works
Self-citationDel‐Aguila, J. L., Fernández, M. V., Jiménez, J. A., Black, K., Ma, S., Deming, Y. K., Carrell, D., Saef, B. A., Initiative, A. D. N., Howells, B., et al. (2015) · Alzheimer s Research & Therapy · doi:10.1186/s13195-015-0154-x · Cited by 25 · see citing works
Poretools: a toolkit for analyzing nanopore sequence dataPreprint
Loman, N. J., & Quinlan, A. R. (2014) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/007401 · Cited by 16 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Alzheimer 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-citationInflammation: 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
Long-Read Sequencing Emerging in Medical Genetics
Mantere, T., Kersten, S., & Hoischen, A. (2019) · Frontiers in Genetics · doi:10.3389/fgene.2019.00426 · Cited by 430 · see citing works
A guide for the diagnosis of rare and undiagnosed disease: beyond the exome
Marwaha, S., Knowles, J. W., & Ashley, E. A. (2022) · Genome Medicine · doi:10.1186/s13073-022-01026-w · Cited by 365 · see citing works
The role of ABCA7 in Alzheimer’s disease: evidence from genomics, transcriptomics and methylomics
De Roeck, A., Van Broeckhoven, C., & Sleegers, K. (2019) · Acta Neuropathologica · doi:10.1007/s00401-019-01994-1 · Cited by 212 · see citing works
Self-citationUnderstanding Alzheimer Disease at the Interface between Genetics and Transcriptomics
Verheijen, J., & Sleegers, K. (2018) · Trends in Genetics · doi:10.1016/j.tig.2018.02.007 · Cited by 189 · see citing works
Self-citationA global view of the genetic basis of Alzheimer disease
Reitz, C., Pericak-Vance, M., Foroud, T., & Mayeux, R. (2023) · Nature Reviews Neurology · doi:10.1038/s41582-023-00789-z · Cited by 143 · see citing works
Dissecting the clinical heterogeneity of early-onset Alzheimer’s disease
Sirkis, D. W., Bonham, L. W., Johnson, T. P., La Joie, R., & Yokoyama, J. S. (2022) · Molecular Psychiatry · doi:10.1038/s41380-022-01531-9 · Cited by 151 · see citing works
The third generation sequencing: the advanced approach to genetic diseases
Xiao, T., & Zhou, W. (2020) · Translational Pediatrics · doi:10.21037/tp.2020.03.06 · Cited by 142 · see citing works
Beyond the exome: What’s next in diagnostic testing for Mendelian conditions
Wojcik, M. H., Reuter, C. M., Marwaha, S., Mahmoud, M., Duyzend, M., Barseghyan, H., Yuan, B., Boone, P. M., Groopman, E., Délot, E. C., et al. (2023) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2023.06.009 · Cited by 134 · see citing works
ABCA7 and Pathogenic Pathways of Alzheimer’s Disease
Aikawa, T., Holm, M., & Kanekiyo, T. (2018) · Brain Sciences · doi:10.3390/brainsci8020027 · Cited by 124 · see citing works
Alcolea, D. A., Clarimón, J., Carmona‐Iragui, M., Illán‐Gala, I., Morenas‐Rodríguez, E., Barroeta, I., Nogué, R. R., Sala, I., Sánchez‐Saudinós, M. B., Videla, L., et al. (2019) · Alzheimer s & Dementia Translational Research & Clinical Interventions · doi:10.1016/j.trci.2019.09.005 · Cited by 121 · see citing works
Self-citationHoogmartens, J., Cacace, R., & Broeckhoven, C. V. (2021) · Alzheimer s & Dementia Diagnosis Assessment & Disease Monitoring · doi:10.1002/dad2.12155 · Cited by 101 · see citing works
An intronic VNTR affects splicing of ABCA7 and increases risk of Alzheimer’s disease
On Behalf of the BELNEU Consortium, De Roeck, A., Duchateau, L., Van Dongen, J., Cacace, R., Bjerke, M., Van den Bossche, T., Cras, P., Vandenberghe, R., De Deyn, P. P., et al. (2018) · Acta Neuropathologica · doi:10.1007/s00401-018-1841-z · Cited by 93 · see citing works
Self-citationRole of ABCA7 in Human Health and in Alzheimer’s Disease
Dib, S., Pahnke, J., & Gosselet, F. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22094603 · Cited by 86 · see citing works
ABC transporters: human disease and pharmacotherapeutic potential
Moore, J. M., Bell, E. L., Hughes, R. O., & Garfield, A. S. (2022) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2022.11.001 · Cited by 83 · see citing works
The role of alternative splicing coupled to nonsense-mediated mRNA decay in human disease
da Costa, P. J., Menezes, J., & Romão, L. (2017) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2017.07.013 · Cited by 77 · see citing works
Ament, I. H., DeBruyne, N., Wang, F., & Lin, L. (2024) · Molecular Therapy · doi:10.1016/j.ymthe.2024.11.025 · Cited by 71 · see citing works
ABCA7 and the altered lipidostasis hypothesis of Alzheimer's disease
Lyssenko, N. N., & Praticò, D. (2020) · Alzheimer s & Dementia · doi:10.1002/alz.12220 · Cited by 66 · see citing works
Chaves, J. C. S., Dando, S. J., White, A. R., & Oikari, L. E. (2024) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2023.166967 · Cited by 62 · see citing works
Ahmed, H., Wang, Y., Griffiths, W. J., Levey, A. I., Pikuleva, I. A., Liang, S. H., & Haider, A. (2024) · Brain · doi:10.1093/brain/awae028 · Cited by 57 · see citing works
The role of ATP-binding cassette subfamily A in the etiology of Alzheimer’s disease
Bossaerts, L., Cacace, R., & van Broeckhoven, C. (2022) · Molecular Neurodegeneration · doi:10.1186/s13024-022-00536-w · Cited by 50 · see citing works
A review of the potential of the MinION™ single‐molecule sequencing system for forensic applications
Plesivkova, D., Richards, R., & Harbison, S. (2018) · WIREs Forensic Science · doi:10.1002/wfs2.1323 · Cited by 41 · see citing works
Patel, T., Brookes, K. J., Turton, J. C., Chaudhury, S., Guetta‐Baranes, T., Guerreiro, R. J., Brás, J., Hernandez, D. G., Singleton, A., Francis, P. T., et al. (2017) · Neuropathology and Applied Neurobiology · doi:10.1111/nan.12452 · Cited by 46 · see citing works
The microglial lysosomal system in Alzheimer’s disease: Guardian against proteinopathy
Acker, Z. P. V., Perdok, A., Bretou, M., & Annaert, W. G. (2021) · Ageing Research Reviews · doi:10.1016/j.arr.2021.101444 · Cited by 45 · see citing works
The impact of rare genetic variants on Alzheimer disease
Deyn, L. D., & Sleegers, K. (2025) · Nature Reviews Neurology · doi:10.1038/s41582-025-01062-1 · Cited by 43 · see citing works
Self-citationChallenge accepted: uncovering the role of rare genetic variants in Alzheimer’s disease
Khani, M., Gibbons, E., Bras, J., & Guerreiro, R. (2022) · Molecular Neurodegeneration · doi:10.1186/s13024-021-00505-9 · Cited by 39 · see citing works
The ABC's of Alzheimer risk gene ABCA7
Duchateau, L., Wawrzyniak, N., & Sleegers, K. (2024) · Alzheimer s & Dementia · doi:10.1002/alz.13805 · Cited by 33 · see citing works
Self-citationAmyloid-β1–43 cerebrospinal fluid levels and the interpretation of APP, PSEN1 and PSEN2 mutations
Perrone, F., Bjerke, M., Hens, E., Sieben, A., Timmers, M., Roeck, A. D., Vandenberghe, R. R., Sleegers, K., Martin, J., Deyn, P. P. D., et al. (2020) · Alzheimer s Research & Therapy · doi:10.1186/s13195-020-00676-5 · Cited by 28 · see citing works
Self-citationLee, W., Choi, S. H., Shea, M. G., Cheng, P., Dombroski, B. A., Pitsillides, A., Heard‐Costa, N. L., Wang, H., Bulekova, K., Kuzma, A. B., et al. (2024) · Alzheimer s & Dementia · doi:10.1002/alz.14283 · Cited by 27 · see citing works
The roles of SMYD4 in epigenetic regulation of cardiac development in zebrafish
Xiao, D., Wang, H., Hao, L., Guo, X. H., Ma, X., Qian, Y., Chen, H., Ma, J., Zhang, J., Sheng, W., et al. (2018) · PLoS Genetics · doi:10.1371/journal.pgen.1007578 · Cited by 25 · see citing works
Curtis, D., Bakaya, K., Sharma, L., & Bandyopadhyay, S. (2020) · Annals of Human Genetics · doi:10.1111/ahg.12375 · Cited by 24 · see citing works
ABCA7 variants impact phosphatidylcholine and mitochondria in neurons
von Maydell, D., Wright, S. E., Pao, P.-C., Staab, C., King, O., Spitaleri, A., Bonner, J. M., Liu, L., Yu, C. J., Chiu, C.-C., et al. (2025) · Nature · doi:10.1038/s41586-025-09520-y · Cited by 35 · see citing works
Ciani, M., Bonvicini, C., Scassellati, C., Carrara, M., Maj, C., Fostinelli, S., Binetti, G. G., Ghidoni, R., & Benussi, L. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20163903 · Cited by 23 · see citing works
Self-citationBossaerts, L., Hens, E., Cacace, R., Asselbergh, B., & Broeckhoven, C. V. (2022) · Acta Neuropathologica Communications · doi:10.1186/s40478-022-01346-3 · Cited by 21 · see citing works
Specificity of ABCA7-mediated cell lipid efflux
Picataggi, A., Rodrigues, A., Cromley, D. A., Wang, H., Wiener, J. P., Garliyev, V., Billheimer, J. T., Grabiner, B. C., Hurt, J. A., Chen, A. C., et al. (2022) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2022.159157 · Cited by 20 · see citing works
Rare <i>ABCA7</i> variants in 2 German families with Alzheimer disease
May, P., Pichler, S., Hartl, D., Bobbili, D. R., Mayhaus, M., Spaniol, C., Kurz, A., Balling, R., Schneider, J. G., & Riemenschneider, M. (2018) · Neurology Genetics · doi:10.1212/nxg.0000000000000224 · Cited by 18 · see citing works
Long read sequencing overcomes challenges in the diagnosis of SORD neuropathy
Grosz, B. R., Stevanovski, I., Negri, S., Ellis, M., Barnes, S. L., Reddel, S., Vucic, S., Nicholson, G. A., Cortese, A., Kumar, K. R., et al. (2022) · Journal of the Peripheral Nervous System · doi:10.1111/jns.12485 · Cited by 18 · see citing works
Bossaerts, L., Hens, E., Hanseeuw, B. J., Vandenberghe, R. R., Cras, P. P., Deyn, P. P. D., Engelborghs, S., & Broeckhoven, C. V. (2021) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2021.04.023 · Cited by 17 · see citing works
Self-citationWhole‐exome rare‐variant analysis of Alzheimer's disease and related biomarker traits
Küçükali, F., Neumann, A., Dongen, J. V., Pooter, T. D., Joris, G., Rijk, P. D., Ohlei, O., Dobričić, V., Bos, I., Vos, S. J. B., et al. (2022) · Alzheimer s & Dementia · doi:10.1002/alz.12842 · Cited by 16 · see citing works
Self-citationSchlieben, L. D., Prokisch, H., & Yépez, V. A. (2021) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2021.647277 · Cited by 16 · see citing works
Iqbal, J., Suarez, M. D., Yadav, P. K., Walsh, M. T., Li, Y., Wu, Y., Huang, Z., James, A. W., Escobar, V., Mokbe, A., et al. (2022) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2022.102411 · Cited by 16 · see citing works
Clinical Deep Phenotyping of ABCA7 Mutation Carriers
Campbell, A. S., Ho, C. C. G., Atık, M., Allen, M., Lincoln, S., Malphrus, K., Nguyen, T., Oatman, S. R., Corda, M., Conway, O., et al. (2022) · Neurology Genetics · doi:10.1212/nxg.0000000000000655 · Cited by 14 · see citing works
The Abca7V1613M variant reduces Aβ generation, plaque load, and neuronal damage
Butler, C. A., Mendoza‐Arvilla, A., Milinkeviciute, G., Cunha, C. D., Kawauchi, S., Rezaie, N., Liang, H. Y., Javonillo, D. I., Thach, A., Wang, S., et al. (2024) · Alzheimer s & Dementia · doi:10.1002/alz.13783 · Cited by 14 · see citing works
Furlan, M., Tanaka, I., Leonardi, T., de Pretis, S., & Pelizzola, M. (2020) · Frontiers in Genetics · doi:10.3389/fgene.2020.00394 · Cited by 14 · see citing works
Early‐onset Alzheimer's disease explained by polygenic risk of late‐onset disease?
Mantyh, W. G., Cochran, J. N., Taylor, J. W., Broce, I., Geier, E. G., Bonham, L. W., Anderson, A. G., Sirkis, D. W., Joie, R. L., Iaccarino, L., et al. (2023) · Alzheimer s & Dementia Diagnosis Assessment & Disease Monitoring · doi:10.1002/dad2.12482 · Cited by 12 · see citing works
Structural insights into human ABCA7-mediated lipid transport
Fang, S., Wang, L., Cheng, M., Xu, D., Chen, Z., Wang, J., Liao, W., Li, Y., Zhou, C., Hou, W., et al. (2025) · Structure · doi:10.1016/j.str.2024.12.015 · Cited by 12 · see citing works
Dementia-related genetic variants in an Italian population of early-onset Alzheimer’s disease
Bartoletti‐Stella, A., Tarozzi, M. E., Mengozzi, G., Asirelli, F., Brancaleoni, L., Mometto, N., Maserati, M. S., Baiardi, S., Linarello, S., Spallazzi, M., et al. (2022) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2022.969817 · Cited by 12 · see citing works
Curtis, D., Bakaya, K., Sharma, L., & Bandyopadhyay, S. (2019) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/596007 · Cited by 11 · see citing works
Wang, N., Pan, Y., Starling, S. C., Haskell, D. H., Quintero, A. C., Kawatani, K., Inoue, Y., Shue, F., Ma, X., Aikawa, T., et al. (2025) · Alzheimer s & Dementia · doi:10.1002/alz.70112 · Cited by 10 · see citing works
The Early‐Onset Alzheimer's Disease Whole‐Genome Sequencing Project: Study design and methodology
Ray, N. R., Ayodele, T., Jean‐Francois, M. N., Baez, P., Fernández, M. V., Bradley, J. L., Crane, P. K., Dalgard, C. L., Kuzma, A. B., Nicaretta, H. I., et al. (2023) · Alzheimer s & Dementia · doi:10.1002/alz.13370 · Cited by 8 · see citing works
Duchateau, L., Küҫükali, F., Roeck, A. D., Wittens, M. M. J., Temmerman, J., Weets, I., Timmers, M., Engelborghs, S., Bjerke, M., & Sleegers, K. (2023) · Alzheimer s Research & Therapy · doi:10.1186/s13195-023-01338-y · Cited by 8 · see citing works
Self-citationGórska, A. M., Santos‐García, I., Kvasnička, A., Dobešová, D., Friedecký, D., Gildenblat, J., & Pahnke, J. (2026) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2026.102891 · Cited by 5 · see citing works
Long-read sequencing for brain tumors
Shelton, W. J., Zandpazandi, S., Nix, J. S., Gökden, M., Bauer, M., Ryan, K. R., Wardell, C. P., Vaske, O. M., & Rodriguez, A. (2024) · Frontiers in Oncology · doi:10.3389/fonc.2024.1395985 · Cited by 5 · see citing works
SNP-by-CpG Site Interactions in ABCA7 Are Associated with Cognition in Older African Americans
Chaar, D., Nguyen, K. A., Wang, Y.-Z., Ratliff, S. M., Mosley, T. H., Kardia, S. L. R., Smith, J. A., & Zhao, W. (2022) · Genes · doi:10.3390/genes13112150 · Cited by 5 · see citing works
Gan, J., Zhou, H., Liu, C., & Fang, L. (2023) · Neurological Sciences · doi:10.1007/s10072-023-06602-5 · Cited by 5 · see citing works
Third-Generation Cytogenetic Analysis
Magini, P., Mingrino, A., Gega, B., Mattei, G., Semeraro, R., Bolognini, D., Mongelli, P., Desiderio, L., Pittalis, M. C., Pippucci, T., et al. (2022) · Journal of Molecular Diagnostics · doi:10.1016/j.jmoldx.2022.03.013 · Cited by 5 · see citing works
Guo, P., Cao, C., Ma, Y., & Wang, J. (2021) · Journal of Neural Transmission · doi:10.1007/s00702-021-02337-9 · Cited by 3 · see citing works
In Planta Gene Expression and Gene Editing in Moso Bamboo Leaves
Sun, H., Wang, S., & Gao, Z. (2023) · Journal of Visualized Experiments · doi:10.3791/65799 · Cited by 3 · see citing works
ZCWPW1 loss-of-function variants in Alzheimer’s DiseasePreprint
Küçükali, F., Nußbaumer, K., Dongen, J. V., Hens, E., Bellenguez, C., Grenier‐Boley, B., Daian, D., Boland, A., Deleuze, J., Lambert, J., et al. (2021) · medRxiv · doi:10.1101/2021.08.13.21261426 · Cited by 3 · see citing works
Self-citationCellular insights into transposable elements in Alzheimer’s disease
Kumar, V., & Beck, S. (2026) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2025.1642599 · Cited by 2 · see citing works
Garliyev, V., Lyssenko, C. A., Wiener, J. P., Praticò, D., & Lyssenko, N. N. (2024) · Journal of Neuropathology & Experimental Neurology · doi:10.1093/jnen/nlae060 · Cited by 2 · see citing works
Schultheis, N., Connell, A., Kapral, A., Becker, R. J., Mueller, R., Shah, S., O’Donnell, M., Roseman, M., Swanson, L., DeGuara, S., et al. (2024) · iScience · doi:10.1016/j.isci.2024.110256 · Cited by 2 · see citing works
Xi, J., Ding, D., Zhao, Q., Liang, X., Zheng, L., Guo, Q., Hong, Z., Fu, H., Xu, J., & Xiao, Q. (2020) · Current Alzheimer Research · doi:10.2174/1567205017666200317095608 · Cited by 2 · see citing works
Cochran, J. N., McKinley, E., Cochran, M., Amaral, M. D., Moyers, B. A., Lasseigne, B. N., Gray, D. E., Lawlor, J. M. J., Prokop, J. W., Geier, E. G., et al. (2019) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/748046 · Cited by 2 · see citing works
Yan, R. (2019) · Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature · doi:10.3410/f.735170868.793558625 · Cited by 2 · see citing works
Huang, Y., Lu, Y., Song, C., Wei, Y., Yang, Y., Ren, J., Wang, M., Tang, C., Riaz, A., Shah, M. A., et al. (2023) · Journal of Nanoelectronics and Optoelectronics · doi:10.1166/jno.2023.3419 · Cited by 1 · see citing works
Plasma Neurofilament Light Combined with Risk Genes for the Diagnosis of Alzheimer?s Disease
Zhang, S. Z., Mei, F., Gao, M., Zhang, L., Ma, L., Wu, H., Liu, L. X., Cao, M., & He, X. L. (2021) · Indian Journal of Pharmaceutical Sciences · doi:10.36468/pharmaceutical-sciences.spl.322 · Cited by 1 · see citing works
Enigma: An Efficient Model for Deciphering Regulatory GenomicsPreprint
Jung, A., Zhu, H., Li, R., Gao, A. J., Lau, T., Chu, V. S., Lim, D., Cole, C. B., Lee, L. J., Celaj, A., et al. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2025.12.18.694875 · Cited by 1 · see citing works
Duchateau, L., Küҫükali, F., Roeck, A. D., Wittens, M. M. J., Temmerman, J., Weets, I., Timmers, M., Engelborghs, S., Bjerke, M., & Sleegers, K. (2023) · Figshare · doi:10.6084/m9.figshare.24540665
Self-citationAnalysis of transporter activity in an Alzheimer’s disease blood-brain barrier cell model
Chaves, J. (2024) · Queensland University of Technology · doi:10.5204/thesis.eprints.248279
Genetic Research in Alzheimer’s Disease
Tepgeç, F., & Uyguner, Z. O. (2024) · doi:10.69860/nobel.9786053359166.8
Kharrat, M., Bouchaala, W., Mohammed, M. M. D., Issa, A. B., Fakhfakh, F., kamoun, F., & Triki, C. (2025) · Molecular Biology Reports · doi:10.1007/s11033-025-11182-y
Duchateau, L., Küҫükali, F., Roeck, A. D., Wittens, M. M. J., Temmerman, J., Weets, I., Timmers, M., Engelborghs, S., Bjerke, M., & Sleegers, K. (2024) · Figshare · doi:10.6084/m9.figshare.24540868
Self-citationAdvancements in the Study of Missense Mutations in ABCA7 in Alzheimer’s Disease
Liu, L., & Zhu, B. (2026) · Journal of Molecular Neuroscience · doi:10.1007/s12031-026-02526-9
- Authors
- On behalf of the European Early-Onset Dementia (EU EOD) consortium, De Roeck, A., Van den Bossche, T., van der Zee, J., Verheijen, J., De Coster, W., Van Dongen, J., Dillen, L., Baradaran-Heravi, Y., Heeman, B., Sanchez-Valle, R., Lladó, A., Nacmias, B., Sorbi, S., Gelpi, E., Grau-Rivera, O., Gómez-Tortosa, E., Pastor, P., Ortega-Cubero, S., Pastor, M. A., Graff, C., Thonberg, H., Benussi, L., Ghidoni, R., Binetti, G., de Mendonça, A., Martins, M., Borroni, B., Padovani, A., Almeida, M. R., Santana, I., Diehl-Schmid, J., Alexopoulos, P., Clarimon, J., Lleó, A., Fortea, J., Tsolaki, M., Koutroumani, M., Matěj, R., Rohan, Z., De Deyn, P., Engelborghs, S., Cras, P., Van Broeckhoven, C., & Sleegers, K.
- Affiliations
- University of Antwerp (BE)
- Hospital Clínic de Barcelona (ES)
- University of Florence (IT)
- Karolinska University Hospital (SE)
- Centro San Giovanni di Dio Fatebenefratelli (IT)
- University of Lisbon (PT)
- University of Brescia (IT)
- Centro de Neurociências e Biologia Celular (PT)
- Technical University of Munich (DE)
- Universitat Autònoma de Barcelona (ES)
- Aristotle University of Thessaloniki (GR)
- Charles University (CZ)
- Corresponding author
- Sleegers, Kristel
- ORCID
- Verheijen, Jan
- Heeman, Bavo
- Lladó, Albert
- Nacmias, Benedetta
- Sorbi, Sandro
- Graff, Caroline
- Benussi, Luisa
- Ghidoni, Roberta
- Binetti, Giuliano
- Martins, Madalena
- Borroni, Barbara
- Padovani, Alessandro
- Almeida, Maria Rosário
- Santana, Isabel
- Alexopoulos, Panagiotis
- Lleó, Alberto
- Fortea, Juan
- Tsolaki, Magda
- Koutroumani, Maria
- Matěj, Radoslav
- Engelborghs, Sebastiaan
- Cras, Patrick
- Sleegers, Kristel
- Venue
- Acta Neuropathologica
- Published
- 2017-04-27
- Volume
- 134
- Issue
- 3
- Pages
- 475-487
- ISSN
- 0001-6322 (ISSN-L)
- 1432-0533
- PMC
- PMC5563332
- OpenAlex
- W2609657566
- Cited by
- 74
- References
- 52
- Citations by year
- 2026: 3 · 2025: 6 · 2024: 10 · 2023: 10 · 2022: 14 · 2021: 8 · 2020: 6 · 2019: 8 · 2018: 7 · 2017: 2
- FWCI
- 4.65
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Acta Neuropathologica (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Dipòsit Digital de Documents de la UAB (Universitat Autònoma de Barcelona) (submittedVersion, cc-by)
- LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) (submittedVersion, cc-by)
- Florence Research (University of Florence) (submittedVersion, cc-by)
- mediaTUM – the media and publications repository of the Technical University Munich (Technical University Munich) (submittedVersion)
- MPG.PuRe (Max Planck Society) (submittedVersion, other-oa)
- VUBIR (Vrije Universiteit Brussel) (submittedVersion)
- Funders
- Seventh Framework Programme (305299)
- BELSPO (NeuroBrainNet)
- SAO-FRA (S16031, S13023)
- Flemish Government initiated Flanders Impulse Program on Networks for Dementia Research (VIND)
- Flemish Government Initiated Methusalem Excellence Program
- FWO (1S44216N)
- VIB (Technology Fund)
- University of Antwerp Research Fund
- VLAIO (Hermesfonds)
- Generalitat de Catalunya (2014SGR-0235)
- Instituto de Salud Carlos III (PI12/01311)
- Spanish Ministry of Economy and Competitiveness ISCIII (PI14/00282)
- European Regional Development Fund
- Italian Ministry of Health (RF-2010-2319722, Ricerca Corrente)
- Fondazione Cassa di Risparmio di Pistoia e Pescia (2014.0365)
- 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 › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Keywords
- ABCA7, early-onset Alzheimer's disease, nonsense-mediated mRNA decay, alternative splicing, disease penetrance, rare variant association, genetic screening
- MeSH terms
- Adult, Aged, Alzheimer Disease, Female, Humans, Male, Middle Aged, Mutation, Age of Onset, ATP-Binding Cassette Transporters, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide, Genetic Association Studies
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
