On the identification of low allele frequency mosaic mutations in the brains of Alzheimer’s disease patients
Open accessAbstract
INTRODUCTION: The cause of sporadic Alzheimer's disease (AD) remains unclear. Given the growing evidence that protein aggregates can spread in a "prion-like" fashion, we reasoned that a small population of brain cells producing such "prion-like" particles due to a postzygotic acquired mutation would be sufficient to trigger the disease. Deep DNA sequencing technology should in principle allow the detection of such mosaics. METHODS: To detect the somatic mutations of genes causing AD present in a small number of cells, we developed a targeted deep sequencing approach to scrutinize the genomic loci of APP, PSEN1, and PSEN2 genes in DNA extracted from the entorhinal cortex, one of the brain regions showing the earliest signs of AD pathology. We also included the analysis of the MAPT gene because mutations may promote tangle formation. We validated candidate mutations with an independent targeted ultradeep amplicon sequencing technique. RESULTS: We demonstrate that our approach can detect single-nucleotide mosaic variants with a 1% allele frequency and copy number mosaic variants present in as few as 10% of cells. We screened 72 AD and 58 control brain samples and identified three mosaic variants with low allelic frequency (∼1%): two novel MAPT variants in sporadic AD patients and a known PSEN2 variant in a Braak II control subject. Moreover, we detected both novel and known pathogenic nonmosaic heterozygous variants in PSEN1 and PSEN2 in this cohort of sporadic AD patients. DISCUSSION: Our results show that mosaic mutations with low allelic frequencies in AD-relevant genes can be detected in brain-derived DNA, but larger samples need to be investigated before a more definitive conclusion with regard to the pathogenicity of such mosaics can be made.
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Additional somatic mutations in genes known to confer risk for AD such as APP and SORL1 have been identified in the brains of both EOAD and LOAD patients.
“Additional somatic mutations in genes known to confer risk for AD such as APP and SORL1 [237] have been identified in the brains of both EOAD and LOAD patients [238, 239]”
From Genetic architecture of Alzheimer's disease (2020) · cites this paper as [239]
Neurons from AD patients have an enriched number of somatic variations not observed in peripheral DNA.
“neurons from AD patients have been observed to have an enriched number of somatic variations not observed in peripheral DNA [239, 240]”
From Genetic architecture of Alzheimer's disease (2020) · cites this paper as [239]
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The Sequence Alignment/Map format and SAMtools
Li, H., Handsaker, B., Wysoker, A., Fennell, T., Ruan, J., Homer, N., Marth, G., Abecasis, G., Durbin, R., & 1000 Genome Project Data Processing Subgroup (2009) · Bioinformatics · doi:10.1093/bioinformatics/btp352 · Cited by 62,041 · 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
The Genome Analysis Toolkit: A MapReduce framework for analyzing next-generation DNA sequencing data
McKenna, A., Hanna, M., Banks, E., Sivachenko, A., Cibulskis, K., Kernytsky, A., Garimella, K., Altshuler, D., Gabriel, S., Daly, M., et al. (2010) · Genome Research · doi:10.1101/gr.107524.110 · Cited by 27,895 · see citing works
Neuropathological stageing of Alzheimer-related changes.
Braak, H., & Braak, E. (1991) · Acta Neuropathologica · doi:10.1007/bf00308809 · Cited by 16,123 · see citing works
ANNOVAR: functional annotation of genetic variants from high-throughput sequencing data
Wang, K., Li, M., & Hakonarson, H. H. (2010) · Nucleic Acids Research · doi:10.1093/nar/gkq603 · Cited by 14,380 · see citing works
A method and server for predicting damaging missense mutations.
Adzhubei, I. A., Schmidt, S., Peshkin, L., Ramensky, V. E., Gerasimova, A., Bork, P., Kondrashov, A. S., & Sunyaev, S. R. (2010) · Nature Methods · doi:10.1038/nmeth0410-248 · Cited by 13,194 · see citing works
VarScan 2: Somatic mutation and copy number alteration discovery in cancer by exome sequencingPreprint
Koboldt, D. C., Zhang, Q., Larson, D. E., Shen, D., McLellan, M. D., Lin, L., Miller, C. A., Mardis, E. R., Ding, L., & Wilson, R. K. (2012) · Genome Research · doi:10.1101/gr.129684.111 · Cited by 4,822 · see citing works
Cloning of a gene bearing missense mutations in early-onset familial Alzheimer's disease
Sherrington, R., Rogaev, E. I., Liang, Y., Rogaeva, E. A., Levesque, G., Ikeda, M., Chi, H., Lin, C., Li, G., Holman, K., et al. (1995) · Nature · doi:10.1038/375754a0 · Cited by 4,051 · see citing works
Stratton, M. R., Campbell, P. J., & Futreal, P. A. (2009) · Nature · doi:10.1038/nature07943 · Cited by 3,459 · see citing works
Predicting Deleterious Amino Acid SubstitutionsPreprint
Ng, P. C., & Henikoff, S. (2001) · Genome Research · doi:10.1101/gr.176601 · Cited by 2,667 · see citing works
Azevedo, F. A. C., Carvalho, L. R. B., Grinberg, L. T., Farfel, J. M., Ferretti, R. E. L., Leite, R. E. P., Filho, W. J., Lent, R., & Herculano‐Houzel, S. (2009) · Journal of Comparative Neurology · doi:10.1002/cne.21974 · Cited by 2,337 · see citing works
Melnick, V. L., & Dubler, N. N. (1985) · Contemporary Issues in Biomedicine, Ethics, and Society · doi:10.1007/978-1-4612-5174-3 · Cited by 1,986 · see citing works
Transmission and spreading of tauopathy in transgenic mouse brain
Clavaguera, F., Bolmont, T., Crowther, R. A., Abramowski, D., Frank, S., Probst, A., Fraser, G., Stalder, A. K., Beibel, M., Staufenbiel, M., et al. (2009) · Nature Cell Biology · doi:10.1038/ncb1901 · Cited by 1,803 · see citing works
Propagation of Tau Pathology in a Model of Early Alzheimer's Disease
de Calignon, A., Polydoro, M., Suárez-Calvet, M., William, C., Adamowicz, D. H., Kopeikina, K. J., Pitstick, R., Sahara, N., Ashe, K. H., Carlson, G. A., et al. (2012) · Neuron · doi:10.1016/j.neuron.2011.11.033 · Cited by 1,427 · see citing works
Campion, D., Dumanchin, C., Hannequin, D., Dubois, B., Belliard, S., Puel, M., Thomas-Anterion, C., Michon, A., Martin, C., Charbonnier, F., et al. (1999) · The American Journal of Human Genetics · doi:10.1086/302553 · Cited by 785 · see citing works
The Genetics of Alzheimer's Disease
Bertram, L., & Tanzi, R. E. (2012) · Progress in molecular biology and translational science · doi:10.1016/b978-0-12-385883-2.00008-4 · Cited by 784 · see citing works
De novo somatic mutations in components of the PI3K-AKT3-mTOR pathway cause hemimegalencephaly
Lee, J. H., Huynh, M., Silhavy, J. L., Kim, S., Dixon-Salazar, T., Heiberg, A., Scott, E., Bafna, V., Hill, K. J., Collazo, A., et al. (2012) · Nature Genetics · doi:10.1038/ng.2329 · Cited by 703 · see citing works
Evolution of the cancer genome
Yates, L. R., & Campbell, P. J. (2012) · Nature Reviews Genetics · doi:10.1038/nrg3317 · Cited by 645 · see citing works
A genomic view of mosaicism and human disease
Biesecker, L. G., & Spinner, N. B. (2013) · Nature Reviews Genetics · doi:10.1038/nrg3424 · Cited by 623 · see citing works
Somatic mutation, genomic variation, and neurological disease
Poduri, A., Evrony, G. D., Cai, X., & Walsh, C. A. (2013) · Science · doi:10.1126/science.1237758 · Cited by 584 · see citing works
Peripherally Applied Aβ-Containing Inoculates Induce Cerebral β-Amyloidosis
Eisele, Y. S., Obermüller, U., Heilbronner, G., Baumann, F., Kaeser, S. A., Wolburg, H., Walker, L. C., Staufenbiel, M., Heikenwalder, M., & Jucker, M. (2010) · Science · doi:10.1126/science.1194516 · Cited by 568 · see citing works
Linking Aβ and Tau in Late-Onset Alzheimer's Disease: A Dual Pathway Hypothesis
Small, S. A., & Duff, K. (2008) · Neuron · doi:10.1016/j.neuron.2008.11.007 · Cited by 546 · see citing works
D'Souza, I., Poorkaj, P., Hong, M., Nochlin, D., Lee, V., Bird, T., & Schellenberg, G. (1999) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.96.10.5598 · Cited by 545 · see citing works
Tsiatis, A. C., Norris-Kirby, A., Rich, R. G., Hafez, M. J., Gocke, C. D., Eshleman, J. R., & Murphy, K. M. (2010) · Journal of Molecular Diagnostics · doi:10.2353/jmoldx.2010.090188 · Cited by 488 · see citing works
Emerging patterns of somatic mutations in cancer
Watson, I. R., Takahashi, K., Futreal, P. A., & Chin, L. (2013) · Nature Reviews Genetics · doi:10.1038/nrg3539 · Cited by 481 · see citing works
Somatic activation of AKT3 causes hemispheric developmental brain malformations
Poduri, A., Evrony, G. D., Cai, X., Elhosary, P. C., Beroukhim, R., Lehtinen, M. K., Hills, L. B., Heinzen, E. L., Hill, A., Hill, R. S., et al. (2012) · Neuron · doi:10.1016/j.neuron.2012.03.010 · Cited by 478 · see citing works
Conlin, L. K., Thiel, B. D., Bönnemann, C. G., Medne, L., Ernst, L. M., Zackai, E. H., Deardorff, M. A., Krantz, I. D., Hakonarson, H. H., & Spinner, N. B. (2010) · Human Molecular Genetics · doi:10.1093/hmg/ddq003 · Cited by 475 · see citing works
The Transcellular Spread of Cytosolic Amyloids, Prions, and Prionoids
Aguzzi, A., & Rajendran, L. (2009) · Neuron · doi:10.1016/j.neuron.2009.12.016 · Cited by 407 · see citing works
Kane, M. D., Lipinski, W. J., Callahan, M. J., Bian, F., Durham, R. A., Schwarz, R. D., Roher, A. E., & Walker, L. C. (2000) · The Journal of Neuroscience · doi:10.1523/jneurosci.20-10-03606.2000 · Cited by 394 · see citing works
Somatic mutations in cerebral cortical malformations
Jamuar, S. S., Lam, A.-T. N., Kircher, M., D’Gama, A. M., Wang, J., Barry, B. J., Zhang, X., Hill, R. S., Partlow, J. N., Rozzo, A., et al. (2014) · New England Journal of Medicine · doi:10.1056/nejmoa1314432 · Cited by 392 · see citing works
Genome sequencing of normal cells reveals developmental lineages and mutational processes
Behjati, S., Huch, M., van Boxtel, R., Karthaus, W., Wedge, D., Tamuri, A. U., Martincorena, I., Petljak, M., Alexandrov, L., Gundem, G., et al. (2014) · Nature · doi:10.1038/nature13448 · Cited by 342 · see citing works
Improving SNP discovery by base alignment quality
Li, H. (2011) · Bioinformatics · doi:10.1093/bioinformatics/btr076 · Cited by 321 · see citing works
Cruchaga, C., Chakraverty, S., Mayo, K., Vallania, F. L. M., Mitra, R. D., Faber, K., Williamson, J., Bird, T., Diaz-Arrastia, R., Foroud, T. M., et al. (2012) · PLoS ONE · doi:10.1371/journal.pone.0031039 · Cited by 320 · see citing works
Cai, X., Evrony, G. D., Lehmann, H. S., Elhosary, P. C., Mehta, B. K., Poduri, A., & Walsh, C. A. (2014) · Cell Reports · doi:10.1016/j.celrep.2014.07.043 · Cited by 318 · see citing works
Mutations of the presenilin I gene in families with early-onset Alzheimer's disease
Campion, D., Flaman, J., Brice, A., Hannequin, D., Dubois, B., Martin, C., Moreau, V., Charbonnier, F., Didierjean, O., Tardieu, S., et al. (1995) · Human Molecular Genetics · doi:10.1093/hmg/4.12.2373 · Cited by 277 · see citing works
Generation of neuronal variability and complexity
Muotri, A. R., & Gage, F. H. (2006) · Nature · doi:10.1038/nature04959 · Cited by 271 · see citing works
Frank, S. A. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0909343106 · Cited by 185 · see citing works
Aneuploid neurons are functionally active and integrated into brain circuitry
Kingsbury, M. A., Friedman, B., McConnell, M. J., Rehen, S. K., Yang, A. H., Kaushal, D., & Chun, J. J. M. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0408171102 · Cited by 175 · see citing works
The Diverse Genetic Landscape of Neurodevelopmental Disorders
Hu, W. F., Chahrour, M. H., & Walsh, C. A. (2014) · Annual Review of Genomics and Human Genetics · doi:10.1146/annurev-genom-090413-025600 · Cited by 169 · see citing works
Jin, S. C., Pástor, P., Cooper, B., Cervantes, S., Benítez, B. A., Razquín, C., Goate, A., Ibero-American Alzheimer Disease Genetics Group Researchers, & Cruchaga, C. (2012) · Alzheimer s Research & Therapy · doi:10.1186/alzrt137 · Cited by 103 · see citing works
Somatic and germline mosaicism in sporadic early-onset Alzheimer's disease
Beck, J. A. (2004) · Human Molecular Genetics · doi:10.1093/hmg/ddh134 · Cited by 102 · see citing works
APP locus duplication in a Finnish family with dementia and intracerebral haemorrhage
Rovelet‐Lecrux, A., Frébourg, T., Tuominen, H. J., Majamaa, K., Campion, D., & Remes, A. M. (2007) · Journal of Neurology Neurosurgery & Psychiatry · doi:10.1136/jnnp.2006.113514 · Cited by 95 · see citing works
Somatic alpha‐synuclein mutations in Parkinson's disease: Hypothesis and preliminary data
Proukakis, C., Houlden, H., & Schapira, A. H. V. (2013) · Movement Disorders · doi:10.1002/mds.25502 · Cited by 72 · see citing works
Sassi, C., Guerreiro, R. J., Gibbs, J. R., Ding, J., Lupton, M. K., Troakes, C., Al‐Sarraj, S., Niblock, M., Gallo, J., Adnan, J., et al. (2014) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2014.06.002 · Cited by 66 · see citing works
The PSEN1, p.E318G Variant Increases the Risk of Alzheimer's Disease in APOE-ε4 Carriers
Benítez, B. A., Karch, C. M. M., Cai, Y., Jin, S. C., Cooper, B., Carrell, D., Bertelsen, S. E., Chibnik, L. B., Schneider, J. A., Bennett, D., et al. (2013) · PLoS Genetics · doi:10.1371/journal.pgen.1003685 · Cited by 64 · see citing works
Stead, L. F., Sutton, K., Taylor, G. R., Quirke, P., & Rabbitts, P. H. (2013) · Human Mutation · doi:10.1002/humu.22365 · Cited by 57 · see citing works
Identification of New Presenilin Gene Mutations in Early-Onset Familial Alzheimer Disease
Tedde, A., Nacmias, B., Ciantelli, M., Forleo, P., Cellini, E., Bagnoli, S., Piccini, C., Caffarra, P., Ghidoni, E., Paganini, M., et al. (2003) · Archives of Neurology · doi:10.1001/archneur.60.11.1541 · Cited by 49 · see citing works
Sassi, C., Guerreiro, R. J., Gibbs, J. R., Ding, J., Lupton, M. K., Troakes, C., Lunnon, K., Al‐Sarraj, S., Brown, K. S., Medway, C., et al. (2014) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2014.04.026 · Cited by 37 · see citing works
Somatic mutation: a cause of sporadic neurodegenerative diseases?
Pamphlett, R. (2004) · Medical Hypotheses · doi:10.1016/j.mehy.2003.11.023 · Cited by 28 · see citing works
Presenilin 2 Ser130Leu mutation in a case of late-onset “sporadic” Alzheimer’s disease
Tomaino, C., Bernardi, L., Anfossi, M., Costanzo, A., Ferrise, F., Gallo, M., Geracitano, S., Maletta, R., Curcio, S. A. M., Mirabelli, M., et al. (2007) · Journal of Neurology · doi:10.1007/s00415-006-0373-y · Cited by 22 · see citing works
Principles of Molecular Disease: Lessons from the Hemoglobinopathies
Nussbaum, R. L., McInnes, R. R., Willard, H. F., & Hamosh, A. (2007) · Elsevier eBooks · doi:10.1016/b978-1-4160-3080-5.50014-6 · Cited by 20 · see citing works
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Research works printed but not linked: 1
- Nussbaum R, McInnes R, Willard H. Thompson & Thompson genetics in medicine. 7th Edition. Elsevier; 2007. Q15
Cited by
Sorted by citations
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
Arendt, T., Stieler, J. T., & Holzer, M. (2016) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2016.08.018 · Cited by 609 · see citing works
Somatic genomic changes in single Alzheimer’s disease neurons
Miller, M. B., Huang, A. Y., Kim, J., Zhou, Z., Kirkham, S. L., Maury, E. A., Ziegenfuss, J. S., Reed, H. C., Neil, J. E., Rento, L., et al. (2022) · Nature · doi:10.1038/s41586-022-04640-1 · Cited by 223 · see citing works
NGS Technologies as a Turning Point in Rare Disease Research , Diagnosis and Treatment
Marmiesse, A. F., Gouveia, S., & Couce, M. L. (2017) · Current Medicinal Chemistry · doi:10.2174/0929867324666170718101946 · Cited by 180 · 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
Peng, Y., Gao, P., Shi, L., Chen, L., Liu, J., & Long, J. (2020) · Antioxidants & Redox Signaling · doi:10.1089/ars.2019.7763 · Cited by 110 · see citing works
Hoogmartens, 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
Genomic mosaicism in the developing and adult brain
Rohrback, S., Siddoway, B. A., Liu, C. S., & Chun, J. J. M. (2018) · Developmental Neurobiology · doi:10.1002/dneu.22626 · Cited by 103 · see citing works
Genomics 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
Prions and Protein Assemblies that Convey Biological Information in Health and Disease
Sanders, D. W., Kaufman, S. K., Holmes, B. B., & Diamond, M. I. (2016) · Neuron · doi:10.1016/j.neuron.2016.01.026 · Cited by 90 · see citing works
Review: Somatic mutations in neurodegeneration
Leija‐Salazar, M., Piette, C. E., & Proukakis, C. (2018) · Neuropathology and Applied Neurobiology · doi:10.1111/nan.12465 · Cited by 84 · see citing works
Somatic variants in autosomal dominant genes are a rare cause of sporadic Alzheimer’s disease
Nicolas, G., Acuña‐Hidalgo, R., Keogh, M. J., Quenez, O., Steehouwer, M., Lelieveld, S., Rousseau, S., Richard, A., Oud, M. S., Marguet, F., et al. (2018) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2018.06.3056 · Cited by 81 · see citing works
Dou, Y., Yang, X., Li, Z., Wang, S., Zhang, Z., Ye, A. Y., Yan, L., Yang, C., Wu, Q., Li, J., et al. (2017) · Human Mutation · doi:10.1002/humu.23255 · Cited by 73 · see citing works
Seed-induced acceleration of amyloid-β mediated neurotoxicity in vivo
Sowade, R. F., & Jahn, T. R. (2017) · Nature Communications · doi:10.1038/s41467-017-00579-4 · Cited by 75 · see citing works
Mokretar, K., Pease, D., Taanman, J., Soenmez, A., Ejaz, A., Lashley, T., Ling, H., Gentleman, S., Houlden, H., Holton, J. L., et al. (2018) · Brain · doi:10.1093/brain/awy157 · Cited by 74 · see citing works
Brain Somatic Mutation in Aging and Alzheimer's Disease
Miller, M. B., Reed, H., & Walsh, C. A. (2021) · Annual Review of Genomics and Human Genetics · doi:10.1146/annurev-genom-121520-081242 · Cited by 56 · see citing works
Lodato, M. A., & Walsh, C. A. (2019) · Human Molecular Genetics · doi:10.1093/hmg/ddz191 · Cited by 56 · see citing works
Somatic mutations in neurons during aging and neurodegeneration
Verheijen, B. M., Vermulst, M., & van Leeuwen, F. W. (2018) · Acta Neuropathologica · doi:10.1007/s00401-018-1850-y · Cited by 57 · see citing works
Somatic mutations in neurodegeneration: An update
Proukakis, C. (2020) · Neurobiology of Disease · doi:10.1016/j.nbd.2020.105021 · Cited by 53 · see citing works
Blauwendraat, C., Wilke, C., Jansen, I. E., Schulte, C., Simón‐Sánchez, J., Metzger, F. G., Bender, B., Gasser, T., Maetzler, W., Rizzu, P., et al. (2015) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2015.09.016 · Cited by 51 · see citing works
The role of de novo mutations in adult-onset neurodegenerative disorders
Nicolas, G., & Veltman, J. A. (2018) · Acta Neuropathologica · doi:10.1007/s00401-018-1939-3 · Cited by 51 · see citing works
Discovery and validation of autosomal dominant Alzheimer’s disease mutations
Dominantly Inherited Alzheimer Network (DIAN), Hsu, S., Gordon, B. A., Hornbeck, R. C., Norton, J. B., Levitch, D., Louden, A., Ziegemeier, E., Laforce, R. J., Chhatwal, J. P., et al. (2018) · Alzheimer s Research & Therapy · doi:10.1186/s13195-018-0392-9 · Cited by 49 · see citing works
Somatic mutations in the human brain: implications for psychiatric research
Nishioka, M., Bundo, M., Iwamoto, K., & Kato, T. (2018) · Molecular Psychiatry · doi:10.1038/s41380-018-0129-y · Cited by 47 · see citing works
Fragola, G., Mabb, A. M., Taylor‐Blake, B., Niehaus, J. K., Chronister, W. D., Mao, H., Simon, J. M., Yuan, H., Li, Z., McConnell, M. J., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-15794-9 · Cited by 40 · see citing works
Challenge 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
Modeling Alzheimer’s disease with human iPS cells: advancements, lessons, and applications
Essayan-Perez, S., Zhou, B., Nabet, A. M., Wernig, M., & Huang, Y. A. (2019) · Neurobiology of Disease · doi:10.1016/j.nbd.2019.104503 · Cited by 37 · see citing works
Genomic Mosaicism Formed by Somatic Variation in the Aging and Diseased Brain
Costantino, I. M., Nicodemus, J., & Chun, J. J. M. (2021) · Genes · doi:10.3390/genes12071071 · Cited by 33 · see citing works
Somatic mutations in disorders with disrupted brain connectivity
Lee, J. H. (2016) · Experimental & Molecular Medicine · doi:10.1038/emm.2016.53 · Cited by 29 · see citing works
Toward common mechanisms for risk factors in Alzheimer's syndrome
Medina, M., Khachaturian, Z. S., Rossor, M. N., Ávila, J., & Cedazo-Mı́nguez, Á. (2017) · Alzheimer s & Dementia Translational Research & Clinical Interventions · doi:10.1016/j.trci.2017.08.009 · Cited by 29 · see citing works
Helgadóttir, H., Lundin, P., Arzt, E. W., Lindström, A.-K., Graff, C., & Eriksson, M. (2019) · Human Molecular Genetics · doi:10.1093/hmg/ddz085 · Cited by 23 · see citing works
SomaticTARDBPvariants as a cause of semantic dementia
van Rooij, J., Mol, M. O., Melhem, S., van der Wal, P., Arp, P., Paron, F., Kaat, L. D., Seelaar, H., Bank, N. B., Miedema, S. S. M., et al. (2020) · Brain · doi:10.1093/brain/awaa317 · Cited by 24 · see citing works
Targeting Tau to Treat Clinical Features of Huntington's Disease
Masnata, M., Salem, S., Jacquet, A. D. R., Anwer, M., & Cicchetti, F. (2020) · Frontiers in Neurology · doi:10.3389/fneur.2020.580732 · Cited by 23 · see citing works
Causes and Consequences of Genome Instability in Psychiatric and Neurodegenerative Diseases
Iourov, I. Y., Vorsanova, S. G., Куринная, О. С., Zelenova, M. A., Vasin, K. S., & Yurov, Y. B. (2021) · Molecular Biology · doi:10.1134/s0026893321010155 · Cited by 20 · see citing works
Distinct X-chromosome SNVs from some sporadic AD samples
Gómez‐Ramos, A., Podlesniy, P., Soriano, E., & Ávila, J. (2015) · Scientific Reports · doi:10.1038/srep18012 · Cited by 19 · see citing works
Tracing brain genotoxic stress in Parkinson’s disease with a novel single-cell genetic sensor
El-Saadi, M. W., Tian, X., Grames, M. S., Ren, M., Keys, K., Li, H., Knott, E. L., Yin, H., Huang, S., & Lu, X. (2022) · Science Advances · doi:10.1126/sciadv.abd1700 · Cited by 18 · see citing works
Horebeek, L. V., Hilven, K., Mallants, K., van Nieuwenhuijze, A. E. M., Kelkka, T., Savola, P., Mustjoki, S. M., Schlenner, S., Liston, A., Dubois, B., et al. (2018) · Human Molecular Genetics · doi:10.1093/hmg/ddy425 · Cited by 17 · see citing works
Somatic mosaicism in the diseased brain
Iourov, I. Y., Vorsanova, S. G., Куринная, О. С., Kutsev, S. I., & Yurov, Y. B. (2022) · Molecular Cytogenetics · doi:10.1186/s13039-022-00624-y · Cited by 17 · see citing works
Single neuron transcriptome analysis can reveal more than cell type classification
Harbom, L. J., Chronister, W. D., & McConnell, M. J. (2016) · BioEssays · doi:10.1002/bies.201500097 · Cited by 15 · see citing works
Genetic Study of Alzheimer’s Disease in Saudi Population
Bitar, F. E., Qadi, N., Rajeh, S. A., Majrashi, A., Abdulaziz, S., Majrashi, N., Inizi, M. A., Taher, A., & Tassan, N. A. A. (2019) · Journal of Alzheimer s Disease · doi:10.3233/jad-180415 · Cited by 15 · see citing works
Min, S., Li, Z.-C., Shieh, A. W., Giase, G., Bao, R., Zhang, C., Kuney, L., Kopp, R., Asif, H., Alliey-Rodriguez, N., et al. (2021) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2021.07.010 · Cited by 11 · see citing works
Reply to: APP gene copy number changes reflect exogenous contamination
Lee, M.-H., Liu, C. S., Zhu, Y., Kaeser, G. E., Rivera, R. R., Romanow, W. J., Kihara, Y., & Chun, J. J. M. (2020) · Nature · doi:10.1038/s41586-020-2523-2 · Cited by 14 · see citing works
Li, Z., Min, S., Alliey‐Rodriguez, N., Giase, G. M., Cheng, L., Craig, D. W., Faulkner, G. J., Asif, H., Liu, C., & Gershon, E. S. (2022) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2022.12.002 · Cited by 13 · see citing works
Причины и последствия геномной нестабильности при психических и нейродегенеративных заболеваниях
Yurov, Y. B., Vorsanova, S. G., Куринная, О. С., Zelenova, M. A., Vasin, K. S., & Yurov, Y. B. (2020) · Molecular Biology · doi:10.31857/s0026898421010158 · Cited by 13 · see citing works
Leija-Salazar, M., Pittman, A., Mokretar, K., Morris, H., Schapira, A., & Proukakis, C. (2020) · Frontiers in Neurology · doi:10.3389/fneur.2020.570424 · Cited by 11 · see citing works
Nishioka, M., Bundo, M., Ueda, J., Katsuoka, F., Sato, Y., Kuroki, Y., Ishii, T., Ukai, W., Murayama, S., Hashimoto, E., et al. (2017) · Psychiatry and Clinical Neurosciences · doi:10.1111/pcn.12632 · Cited by 11 · see citing works
Yang, Y., Bagyinszky, E., & An, S. S. A. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms242015461 · Cited by 10 · see citing works
The genetic landscape of early‐onset Alzheimer's disease in China
Qin, W. D., Li, F., Liu, W., Li, Y., Cao, S., Wei, Y., Li, Y., Wang, Y., Wang, Q., & Jia, J. (2025) · Alzheimer s & Dementia · doi:10.1002/alz.14486 · Cited by 9 · see citing works
New Beginnings in Alzheimer’s Disease: The Most Prevalent Tauopathy
Hernández, F., Llorens-Martı́n, M., Bolós, M., Pérez, M., Cuadros, R., Pallas‐Bazarra, N., Zabala, J. C., & Ávila, J. (2018) · Journal of Alzheimer s Disease · doi:10.3233/jad-179916 · Cited by 9 · see citing works
Limitations and Applications of Rodent Models in Tauopathy and Synucleinopathy Research
Szegvari, E., Holec, S. A. M., & Woerman, A. L. (2025) · Journal of Neurochemistry · doi:10.1111/jnc.70021 · Cited by 8 · see citing works
Assessment of the gene mosaicism burden in blood and its implications for immune disorders
Solís-Moruno, M., Mensa‐Vilaró, A., Batlle-Masó, L., Lobón, I., Bonet, N., Marquès‐Bonet, T., Aróstegui, J. I., & Casals, F. (2021) · Scientific Reports · doi:10.1038/s41598-021-92381-y · Cited by 8 · see citing works
Gómez‐Ramos, A., Picher, Á. J., García, E., Garrido, P. I., Hernández, F., Soriano, E., & Ávila, J. (2017) · Journal of Alzheimer s Disease · doi:10.3233/jad-161053 · Cited by 7 · see citing works
Alzheimer's Disease; Mechanism, Mutations, and Applications of Nano-Medicine.
Maisam, M., Khan, M. T., Lodhi, M. S., Mou, K., Liu, Z.-L., & Wei, D.-Q. (2023) · Frontiers in Bioscience · doi:10.31083/j.fbl2810258 · Cited by 7 · see citing works
La transconformation protéique, nouveau paradigme en neurologie
Hauw, J., Haı̈k, S., & Duyckaerts, C. J. (2015) · Revue Neurologique · doi:10.1016/j.neurol.2015.09.010 · Cited by 6 · see citing works
Brain somatic mutations as RNA therapeutic targets in neurological disorders
Lee, S., & Lee, J. H. (2022) · Annals of the New York Academy of Sciences · doi:10.1111/nyas.14786 · Cited by 5 · see citing works
FTLD-MAPT mutations and short 5′UTR Tau mRNAs increase Tau translation
da Costa, P. J., Perret, A., Buée, L., Hamdane, M., & Martin, F. (2024) · NAR Molecular Medicine · doi:10.1093/narmme/ugae023 · Cited by 4 · see citing works
McDonough, G. A., Cheng, Y., Morillo, K. S., Doan, R. N., Zhou, Z., Kenny, C. J., Foutz, A., Kim, C., Cohen, M. L., Appleby, B. S., et al. (2024) · Acta Neuropathologica · doi:10.1007/s00401-024-02774-2 · Cited by 5 · see citing works
Identification of Low Allele Frequency Mosaic Mutations in Alzheimer Disease
Frigerio, C. S., Fiers, M., Voet, T., & de Strooper, B. (2017) · Neuromethods · doi:10.1007/978-1-4939-7280-7_17 · Cited by 3 · see citing works
Bae, H., Shim, K. H., Yoo, J., Yang, Y., An, S. S. A., & Kang, M. J. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24087446 · Cited by 3 · see citing works
Park, K. W., An, S. S. A., Bagyinszky, E., & Kim, S. (2017) · Clinical Interventions in Aging · doi:10.2147/cia.s128884 · Cited by 3 · see citing works
Genetic Risk Factors for Sporadic Frontotemporal Dementia
Ferrari, R., Manzoni, C., & Momeni, P. (2018) · Springer eBooks · doi:10.1007/978-3-319-72938-1_9 · Cited by 3 · see citing works
Shim, K.-H., Kang, M. J., Bae, H., Kim, D., Park, J., An, S. S. A., & Jeong, D.-E. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23062967 · Cited by 3 · see citing works
Colin, C., Tang, Y.-H., Teng, M., & Gillis, N. (2025) · Human Genomics · doi:10.1186/s40246-025-00847-1 · Cited by 2 · see citing works
Human Brain Single Nucleotide Polymorphism: Validation of DNA Sequencing
Picher, Á. J., Hernández, F., Budeus, B., Soriano, E., & Ávila, J. (2018) · Journal of Alzheimer s Disease Reports · doi:10.3233/adr-170039 · Cited by 1 · see citing works
McMillan, C. T., & Huey, E. D. (2018) · Neurology · doi:10.1212/wnl.0000000000005112
The ubiquitin-proteasome system in neurodegenerative diseases
Verheijen, L. (2023) · doi:10.26481/dis.20231024lv
Yang, Y., Bagyinszky, E., & An, S. S. A. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25179678
Peripheral blood somatic mosaicism and clonal hematopoiesis across ancestry backgroundsPreprint
Colin, C., Tang, Y.-H., Teng, M., & Gillis, N. (2025) · medRxiv · doi:10.1101/2025.03.21.25324408
Ahmed, M., Volkening, K., McLellan, C., Shoesmith, C. L., Balci, T. B., & Strong, M. J. (2026) · Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration · doi:10.1080/21678421.2026.2655734
Somatic mutations: recent advances in brain aging and neurodegeneration
Oatman, S. R., Huang, A. Y., & Miller, M. B. (2026) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2026.102519
Alzheimer’s disease: genetic background in the era of next-generation sequencing technologies
Lukyova, L., Zaťková, A., Minařík, J., Holesova, Z., Budiš, J., Kucharík, M., Beneš, V., Gazdarica, J., & Szemes, T. (2026) · Brain Communications · doi:10.1093/braincomms/fcag332
- Authors
- Sala Frigerio, C., Lau, P., Troakes, C., Deramecourt, V., Gele, P., Van Loo, P., Voet, T., & De Strooper, B.
- Affiliations
- VIB Center for the Biology of Disease KU Leuven Leuven Belgium
- KU Leuven (BE)
- King's College London (GB)
- Université Lille Nord de France (FR)
- Université Lille Nord de France UDSL Lille France
- Center for Human Genetics KU Leuven Leuven Belgium
- Wellcome Sanger Institute (GB)
- Corresponding author
- Voet, Thierry
- Venue
- Alzheimer's & Dementia
- Publisher
- Wiley
- Published
- 2015-04-28
- Volume
- 11
- Issue
- 11
- Pages
- 1265-1276
- ISSN
- 1552-5260 (ISSN-L)
- 1552-5279
- OpenAlex
- W2005742709
- Cited by
- 71
- References
- 52
- Citations by year
- 2026: 3 · 2025: 4 · 2024: 3 · 2023: 4 · 2022: 7 · 2021: 7 · 2020: 9 · 2019: 5 · 2018: 13 · 2017: 8 · 2016: 5 · 2015: 3
- FWCI
- 7.12
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Alzheimer s & Dementia (publishedVersion)
- PubMed (publishedVersion)
- Lirias (KU Leuven) (submittedVersion, other-oa)
- UCL Discovery (University College London) (submittedVersion)
- Research Portal (King's College London) (submittedVersion)
- Funders
- Fonds voor wetenschappelijk onderzoek
- Methusalem grant
- Advanced ERC grant
- COEN
- Medical Research Council
- Alzheimer's Society
- Alzheimer's Research UK
- 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 › Genomics and Rare Diseases
- Keywords
- Alzheimer's disease, somatic mosaicism
- MeSH terms
- Aged, Aged, 80 and over, Alzheimer Disease, Gene Frequency, Humans, Mosaicism, Mutation, Pilot Projects, Cohort Studies, Amyloid beta-Protein Precursor, tau Proteins, Sequence Analysis, DNA, Entorhinal Cortex, Polymorphism, Single Nucleotide, Presenilin-1, Presenilin-2, DNA Copy Number Variations, High-Throughput Nucleotide Sequencing
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