Somatic and germline mosaicism in sporadic early-onset Alzheimer's disease
Abstract
Alzheimer's disease (AD) is the commonest neurodegenerative disease worldwide. Rare familial cases may be caused by mutations in one of three genes-amyloid precursor protein, presenilin-1 and presenilin-2; however, the molecular basis of >99% of AD cases is unknown. Somatic mutation has been considered to be a mechanism that may account for a proportion of sporadic cases of AD, but to date there has been no evidence for this. We now report a sporadic early-onset patient with AD, and show that this individual is a somatic mosaic for a mutation in the presenilin-1 gene, suggesting a novel molecular mechanism for AD. Quantification of the mosaicism demonstrated the degree of mosaicism at 8% in peripheral lymphocytes and 14% in cerebral cortex in the index patient; a clear gene dosage effect on age of presentation and clinical phenotypic presentation is demonstrated. This finding has important implications for the aetiology of sporadic AD, and for other apparently sporadic neurodegenerative diseases such as Parkinson's disease, motor neuron disease and Creutzfeldt-Jakob disease.
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?
A sporadic AD patient harbored a disease-causative mutation in PSEN1 only in approximately 14% of brain cells.
“the finding of a sporadic AD patient who harbored a disease-causative mutation in PSEN1 only in approximately 14% of brain cells [236]”
From Genetic architecture of Alzheimer's disease (2020) · cites this paper as [236]
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
Corder, E. H., Saunders, A. M., Strittmatter, W. J., Schmechel, D. E., Gaskell, P. C., Small, G. W., Roses, A. D., Haines, J. L., & Pericak-Vance, M. A. (1993) · Science · doi:10.1126/science.8346443 · Cited by 9,429 · see citing works
Goate, A., Chartier-Harlin, M.-C., Mullan, M., Brown, J., Crawford, F., Fidani, L., Giuffra, L., Haynes, A., Irving, N., James, L., et al. (1991) · Nature · doi:10.1038/349704a0 · Cited by 4,659 · see citing works
Analysis of any point mutation in DNA. The amplification refractory mutation system (ARMS)
Newton, C. R., Graham, A., Heptinstall, L., Powell, S. J., Summers, C. W., Kalsheker, N. A., Smith, J. C., & Markham, A. F. (1989) · Nucleic Acids Research · doi:10.1093/nar/17.7.2503 · Cited by 2,476 · see citing works
Rogaev, E. I., Sherrington, R., Rogaeva, E. A., Levesque, G., Ikeda, M., Liang, Y., Chi, H., Lin, C., Holman, K., Tsuda, T., et al. (1995) · Nature · doi:10.1038/376775a0 · Cited by 2,052 · see citing works
Clark, R. F., Hutton, M., Fuldner, M., Froelich, S., Karran, E., Talbot, C., Crook, R., Lendon, C., Prihar, G., He, C., et al. (1995) · Nature Genetics · doi:10.1038/ng1095-219 · Cited by 474 · see citing works
Apolipoprotein E4 allele in a population–based study of early–onset Alzheimer's disease
van Duijn, C. M., de Knijff, P., Cruts, M., Wehnert, A., Havekes, L. M., Albert Hofman, D., & Broeckhoven, C. V. (1994) · Nature Genetics · doi:10.1038/ng0594-74 · Cited by 453 · see citing works
Dipple, K. M., & McCabe, E. R. B. (2000) · The American Journal of Human Genetics · doi:10.1086/302938 · Cited by 418 · see citing works
Mechanisms and consequences of somatic mosaicism in humans
Youssoufian, H., & Pyeritz, R. E. (2002) · Nature Reviews Genetics · doi:10.1038/nrg906 · Cited by 391 · see citing works
Screening for PS1 mutations in a referral-based series of AD cases
Rogaeva, E. A., Fafel, K. C., Song, Y., Medeiros, H., Sato, C., Liang, Y., Richard, E., Rogaev, E. I., Frommelt, P., Sadovnick, A. D., et al. (2001) · Neurology · doi:10.1212/wnl.57.4.621 · Cited by 203 · see citing works
Alzheimer disease γ-secretase: a complex story of GxGD-type presenilin proteases
Haass, C., & Steiner, H. (2002) · Trends in Cell Biology · doi:10.1016/s0962-8924(02)02394-2 · Cited by 165 · see citing works
The Genetics of Adult-Onset Neuropsychiatric Disease: Complexities and Conundra?
Kennedy, J. L., Farrer, L. A., Andreasen, N. C., Mayeux, R. P., & George‐Hyslop, P. S. (2003) · Science · doi:10.1126/science.1092132 · Cited by 149 · see citing works
Chromosome Missegregation and Trisomy 21 Mosaicism in Alzheimer's Disease
Geller, L. N., & Potter, H. (1999) · Neurobiology of Disease · doi:10.1006/nbdi.1999.0236 · Cited by 146 · see citing works
Somatic mosaicism and variable expressivity
Gottlieb, B., Beitel, L. K., & Trifiro, M. A. (2001) · Trends in Genetics · doi:10.1016/s0168-9525(00)02178-8 · Cited by 112 · see citing works
Lee, H. S., Sambuughin, N., Červen̆áková, L., Chapman, J., Pocchiari, M., Litvak, S., Qi, H. Y., Budka, H., del Ser, T., Furukawa, H., et al. (1999) · The American Journal of Human Genetics · doi:10.1086/302340 · Cited by 91 · see citing works
Taddei, K., Kwok, J. B., Kril, J. J., Halliday, G. M., Creasey, H. M., Hallupp, M., Fisher, C., Brooks, W. S., Chung, C., Andrews, C., et al. (1998) · Neuroreport · doi:10.1097/00001756-199810050-00034 · Cited by 62 · see citing works
Mammalian Germ Cells: Birth, Sex, and Immortality.
McLaren, A. L. D. (2001) · Cell Structure and Function · doi:10.1247/csf.26.119 · Cited by 49 · see citing works
Neuropathological Criteria for the Diagnosis of Alzheimer’s Disease: Are We Really Ready Yet?
Ball, M. J., & MURDOCH, G. H. (1997) · Neurobiology of Aging · doi:10.1016/s0197-4580(97)00074-2 · Cited by 28 · see citing works
A codon 129 polymorphism in the PRIP gene
Owen, F., Poulter, M., Collinge, J., & Crow, T. J. (1990) · Nucleic Acids Research · doi:10.1093/nar/18.10.3103 · Cited by 28 · see citing works
Flagged first, then by citations
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
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
Somatic Mutations in the Connexin 40 Gene ( GJA5 ) in Atrial Fibrillation
Gollob, M. H., Jones, D. L., Krahn, A. D., Danis, L., Gong, X., Shao, Q., Liu, X., Veinot, J. P., Tang, A., Stewart, A. F. R., et al. (2006) · New England Journal of Medicine · doi:10.1056/nejmoa052800 · Cited by 543 · see citing works
Pathogenic Mechanisms of Somatic Mutation and Genome Mosaicism in Aging
Vijg, J., & Dong, X. (2020) · Cell · doi:10.1016/j.cell.2020.06.024 · Cited by 230 · see citing works
Krafchak, C. M., Pawar, H. S., Moroi, S. E., Sugar, A., Lichter, P. R., Mackey, D. A., Mian, S. I., Nairus, T. M., Elner, V. M., Schteingart, M. T., et al. (2005) · The American Journal of Human Genetics · doi:10.1086/497348 · Cited by 226 · see citing works
Somatic gene mutation and human disease other than cancer: An update
Erickson, R. P. (2010) · Mutation Research/Reviews in Mutation Research · doi:10.1016/j.mrrev.2010.04.002 · Cited by 211 · 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
Correlating familial Alzheimer’s disease gene mutations with clinical phenotype
Ryan, N. S., & Rossor, M. N. (2010) · Biomarkers in Medicine · doi:10.2217/bmm.09.92 · Cited by 176 · see citing works
Inflammation in Parkinson’s disease: role of glucocorticoids
Herrero, M.-T., Estrada, C., Maatouk, L., & Vyas, S. (2015) · Frontiers in Neuroanatomy · doi:10.3389/fnana.2015.00032 · Cited by 175 · see citing works
“…nervous system (CNS) disorders have been reported, for example, somatic mutation in the presenilin-1 gene associated with Alzheimer’s disease (Beck et al., 2004), in SPG4/SPAST (spastic paraplegia4/spastin) causing spastic paraplegia (Depienne et al., 2007) or MECP2 (methyl CpG binding…”
BackgroundThe genetics of Alzheimer's disease
Bagyinszky, E., Youn, Y. C., An, S. S. A., & Kim, S. (2014) · Clinical Interventions in Aging · doi:10.2147/cia.s51571 · Cited by 173 · see citing works
Detection of mosaicRB1mutations in families with retinoblastoma
Rushlow, D., Piovesan, B., Zhang, K., Prigoda, N. L., Marchong, M. N., Clark, R. D., & Gallie, B. L. (2009) · Human Mutation · doi:10.1002/humu.20940 · Cited by 161 · see citing works
Involvement of the kynurenine pathway in the pathogenesis of Parkinson's disease
Lim, C. K., Fernández-Gomez, F. J., Braidy, N., Estrada, C., Costa, C., Costa, S., Bessede, A., Fernandez-Villalba, E., Zinger, A., Herrero, M. T., et al. (2017) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2015.12.009 · Cited by 159 · see citing works
Parkinson's disease and cancer: two wars, one front
Devine, M. J., Plun‐Favreau, H., & Wood, N. W. (2011) · Nature reviews. Cancer · doi:10.1038/nrc3150 · Cited by 153 · 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
Somatic Mosaicism in the Human Genome
Freed, D. N., Stevens, E. L., & Pevsner, J. (2014) · Genes · doi:10.3390/genes5041064 · Cited by 150 · see citing works
Association of micronucleus frequency with neurodegenerative diseases
Migliore, L., Coppedè, F., Fenech, M. F., & Thomas, P. (2010) · Mutagenesis · doi:10.1093/mutage/geq067 · Cited by 149 · see citing works
Marangi, G., & Traynor, B. J. (2014) · Brain Research · doi:10.1016/j.brainres.2014.10.009 · Cited by 146 · see citing works
Somatic mutations, genome mosaicism, cancer and aging
Vijg, J. (2014) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2014.04.002 · Cited by 134 · 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
“One offspring of the affected patient inherited the PSEN1 mutation in all cells of her body and exhibited signs of dementia by age 27, indicating the degree to which mutations that are expressed throughout the body have a profound effect on disease severity (Beck et al., 2004).”
BackgroundGenetics, Functions, and Clinical Impact of Presenilin-1 (PSEN1) Gene
Bagaria, J., Bagyinszky, E., & An, S. S. A. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms231810970 · Cited by 117 · 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
Mullane, K., & Williams, M. J. (2020) · Biochemical Pharmacology · doi:10.1016/j.bcp.2020.113945 · Cited by 106 · see citing works
Somatic Genome Variations in Health and Disease
Iourov, I. Y., Vorsanova, S. G., & Yurov, Y. B. (2010) · Current Genomics · doi:10.2174/138920210793176065 · Cited by 102 · 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
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
Analysis of LINE-1 Elements in DNA from Postmortem Brains of Individuals with Schizophrenia
Doyle, G. A. R., Crist, R. C., Karatas, E. T., Hammond, M. J., Ewing, A. D., Ferraro, T. N., Hahn, C.-G., & Berrettini, W. H. (2017) · Neuropsychopharmacology · doi:10.1038/npp.2017.115 · Cited by 74 · 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
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 73 · see citing works
Sala Frigerio, C., Lau, P., Troakes, C., Deramecourt, V., Gele, P., Van Loo, P., Voet, T., & De Strooper, B. (2015) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2015.02.007 · Cited by 71 · see citing works
Variable phenotype of Alzheimer’s disease with spastic paraparesis
Karlström, H., Brooks, W. S., Kwok, J. B., Broe, G. A., Kril, J. J., McCann, H., Halliday, G. M., & Schofield, P. R. (2007) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2007.05038.x · Cited by 65 · 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
The Genetics of Very Early Onset Alzheimer Disease
Filley, C. M., Rollins, Y. D., Alan Anderson, C., Arciniegas, D. B., Howard, K. L., Murrell, J. R., Boyer, P. J., Kleinschmidt-DeMasters, B. K., & Ghetti, B. (2007) · Cognitive and Behavioral Neurology · doi:10.1097/wnn.0b013e318145a8c8 · Cited by 53 · 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
Genetics of dementia: Update and guidelines for the clinician
Cohn‐Hokke, P. E., Elting, M. W., Pijnenburg, Y. A. L., & Swieten, J. C. V. (2012) · American Journal of Medical Genetics Part B Neuropsychiatric Genetics · doi:10.1002/ajmg.b.32080 · Cited by 47 · see citing works
Early-onset Alzheimer's disease with a de novo mutation in the presenilin 1 gene
Golan, M. P., Styczyńska, M., Jóźwiak, K., Walecki, J. M., Maruszak, A., Pniewski, J., Ługiewicz, R., Filipek, S., Żekanowski, C., & Barcikowska, M. (2007) · Experimental Neurology · doi:10.1016/j.expneurol.2007.08.016 · Cited by 48 · 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
Alzheimer’s Disease-Related Protein Expression in the Retina of Octodon degus
Du, L. Y., Chang, L., Ardiles, Á. O., Tapia‐Rojas, C., Araya, J., Inestrosa, N. C., Palacios, A. G., & Acosta, M. L. (2015) · PLoS ONE · doi:10.1371/journal.pone.0135499 · Cited by 47 · see citing works
Genetic Mosaics and the Germ Line Lineage
Samuels, M. E., & Friedman, J. M. (2015) · Genes · doi:10.3390/genes6020216 · 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
Additional mechanisms conferring genetic susceptibility to Alzheimer’s disease
Calero, M., Gómez‐Ramos, A., Calero, O., Soriano, E., Ávila, J., & Medina, M. (2015) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2015.00138 · Cited by 33 · see citing works
Susceptibility to Aneuploidy in Young Mothers of Down Syndrome Children
Migliore, L., Migheli, F., & Coppedè, F. (2009) · The Scientific World JOURNAL · doi:10.1100/tsw.2009.122 · Cited by 28 · see citing works
Mitigating age-related somatic mutation burden
Vijg, J., Schumacher, B., Abakir, A., Antonov, M., Bradley, C., Cagan, A., Church, G. M., Gladyshev, V. N., Gorbunova, V. A., Maslov, A. Y., et al. (2023) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2023.04.002 · Cited by 30 · 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
Tian, T., Lei, Y., Chen, Y., Karki, M., Jin, L., Finnell, R. H., Wang, L., & Ren, A. (2020) · Human Genetics · doi:10.1007/s00439-020-02172-0 · Cited by 27 · see citing works
Won, S., Kim, Y., & Jeong, B. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21124246 · 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
Jayadev, S. (2022) · CONTINUUM Lifelong Learning in Neurology · doi:10.1212/con.0000000000001125 · Cited by 21 · 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
Can ALS-Associated C9orf72 Repeat Expansions Be Diagnosed on a Blood DNA Test Alone?
Pamphlett, R., Cheong, P. L., Trent, R. J., & Yu, B. (2013) · PLoS ONE · doi:10.1371/journal.pone.0070007 · Cited by 18 · see citing works
Identification of clinically relevant mosaicism in type I hereditary haemorrhagic telangiectasia
Prigoda, N. L., Matevski, D., Dumitru, D., Piovesan, B., Rushlow, D., & Gallie, B. L. (2011) · Journal of Medical Genetics · doi:10.1136/jmg.2010.088112 · Cited by 18 · see citing works
New approaches for modelling sporadic genetic disease in the mouse
Fisher, E., Lana‐Elola, E., Watson, S. D., Vassiliou, G. S., & Tybulewicz, V. L. J. (2009) · Disease Models & Mechanisms · doi:10.1242/dmm.001644 · Cited by 18 · see citing works
Emerging links between cell competition and Alzheimer's disease
Coelho, D. S., & Moreno, E. (2019) · Journal of Cell Science · doi:10.1242/jcs.231258 · Cited by 18 · see citing works
Genetic Complexity of Early-Onset Alzheimer’s Disease
Ghani, M., Reitz, C., George‐Hyslop, P. S., & Rogaeva, E. A. (2018) · Springer eBooks · doi:10.1007/978-3-319-72938-1_3 · Cited by 14 · see citing works
Evrony, G. D. (2016) · Science · doi:10.1126/science.aak9761 · 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
Recombination as a mechanism for sporadic mutation in the surfactant protein‐C gene
McBee, A., Wegner, D., Carlson, C. S., Wambach, J., Yang, P., Heins, H. B., Saugstad, O. D., Trusgnich, M. A., Watkins-Torry, J. M., Nogee, L. M., et al. (2008) · Pediatric Pulmonology · doi:10.1002/ppul.20782 · Cited by 13 · see citing works
Kumar, S., Yadav, N., Pandey, S., & Thelma, B. K. (2018) · Journal of Genetics · doi:10.1007/s12041-018-0953-5 · Cited by 11 · see citing works
Pathology and Diagnosis of Central Nervous System Infections
Sundaram, C., Shankar, S. K., Thong, W. K., & Pardo‐Villamizar, C. (2011) · Pathology Research International · doi:10.4061/2011/878263 · Cited by 10 · see citing works
Hypothesis: Somatic Mosaicism and Parkinson Disease
Kim, H., & Jeon, B. S. (2014) · Experimental Neurobiology · doi:10.5607/en.2014.23.4.271 · Cited by 9 · see citing works
Lahiri, D. K., & Maloney, B. (2012) · Epigenomics · doi:10.2217/epi.12.60 · Cited by 9 · see citing works
Somatic Mosaicism and Neurological Diseases
Jamuar, S. S., D’Gama, A. M., & Walsh, C. A. (2016) · Elsevier eBooks · doi:10.1016/b978-0-12-800105-9.00012-3 · Cited by 13 · see citing works
Ehn, E., Eisfeldt, J., Laffita‐Mesa, J. M., Thonberg, H., Schoumans, J., Portaankorva, A. M., Viitanen, M. H., Lindstrand, A., Nennesmo, I., & Graff, C. (2025) · Scientific Reports · doi:10.1038/s41598-025-86645-0 · Cited by 9 · 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
Prion protein gene mutation detection using long-read Nanopore sequencing
Kroll, F., Dimitriadis, A., Campbell, T., Darwent, L., Collinge, J., Mead, S., & Viré, E. A. (2022) · Scientific Reports · doi:10.1038/s41598-022-12130-7 · Cited by 8 · see citing works
Won, S., Kim, Y., & Jeong, B. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms241914831 · Cited by 8 · see citing works
An approach to finding brain-situated mutations in sporadic Parkinson's disease
Pamphlett, R., Morahan, J. M., Luquin, N., & Yu, B. (2011) · Parkinsonism & Related Disorders · doi:10.1016/j.parkreldis.2011.08.024 · Cited by 8 · see citing works
Agüero, P., Sainz, M. J., Téllez, R., Lorda, I., Ávila, A., García‐Ribas, G., Rodríguez, P. P., & Gómez‐Tortosa, E. (2021) · Journal of Alzheimer s Disease · doi:10.3233/jad-210420 · Cited by 7 · see citing works
Doğan, M., Eröz, R., Tecellioğlu, M., Gezdirici, A., Çevik, B., & Barış, İ. (2022) · Current Alzheimer Research · doi:10.2174/1567205019666220414101251 · Cited by 7 · see citing works
Dynamic self-guiding analysis of Alzheimer's disease
Kurakin, A. V., & Bredesen, D. E. (2015) · Oncotarget · doi:10.18632/oncotarget.4221 · Cited by 7 · see citing works
Instability of the Octarepeat Region of the Human Prion Protein Gene
Li, B., Qing, L., Yan, J., & Kong, Q. (2011) · PLoS ONE · doi:10.1371/journal.pone.0026635 · Cited by 7 · see citing works
DHPLC can be used to detect low-level mutations in amyotrophic lateral sclerosis
Luquin, N., Yu, B., Trent, R. J., & Pamphlett, R. (2010) · Amyotrophic Lateral Sclerosis · doi:10.3109/17482960802572699 · Cited by 7 · see citing works
Genomic Mosaicism of the Brain: Origin, Impact, and Utility
Graham, J. H., Schlachetzki, J. C. M., Yang, X., & Breuss, M. W. (2023) · Neuroscience Bulletin · doi:10.1007/s12264-023-01124-8 · Cited by 6 · see citing works
Vijg, J., Dong, X., & Zhang, L. (2017) · Experimental Biology and Medicine · doi:10.1177/1535370217717696 · Cited by 6 · see citing works
A newly discovered mechanism driving neuronal mutations in Alzheimer’s disease
Chai, G., & Gleeson, J. G. (2018) · Nature · doi:10.1038/d41586-018-07334-9 · Cited by 6 · see citing works
Dispersion of prion protein deposits around blood vessels in variant Creutzfeldt-Jakob disease.
Armstrong, R. A. (2010) · PubMed · Cited by 5 · see citing works
Brain somatic mutations in Alzheimer’s disease: linking genetic mosaicism to neurodegeneration
Li, Z., Zhang, J., Liu, Z., Yu, L., Yang, C., Zhang, L., Xiang, Z., Hu, F., Brazh, N., Shu, K., et al. (2025) · Molecular Neurodegeneration · doi:10.1186/s13024-025-00895-0 · Cited by 4 · see citing works
Won, S., Kim, Y., & Jeong, B. (2021) · Medicina · doi:10.3390/medicina58010055 · 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
Parkinson's disease: Is it all in the genes?
Engeholm, M., & Gasser, T. (2013) · Movement Disorders · doi:10.1002/mds.25611 · Cited by 3 · see citing works
Laminar Distribution of the Pathological Changes in Sporadic and Variant Creutzfeldt-Jakob Disease
Armstrong, R. A. (2010) · Pathology Research International · doi:10.4061/2011/236346 · Cited by 2 · see citing works
Mosaicism in Traditional Mendelian Diseases
Ting, T. W., Shahdadpuri, R., & Jamuar, S. S. (2015) · Current Genetic Medicine Reports · doi:10.1007/s40142-015-0071-0 · Cited by 2 · see citing works
Variable Phenotype of Alzheimer's Disease with Spastic Paraparesis
Karlström, H., Brooks, W. S., Kwok, J. B., Kril, J. J., Halliday, G. M., & Schofield, P. R. (2005) · Research and perspectives in Alzheimer's disease · doi:10.1007/3-540-26522-8_7 · Cited by 2 · see citing works
The emergence of genotypic divergence and future precision medicine applications
Kauffman, M., & Calderon, V. S. (2023) · Handbook of clinical neurology · doi:10.1016/b978-0-323-85538-9.00013-4 · Cited by 1 · see citing works
Choi, E., Jang, B., Ishigami, A., Maruyama, N., Carp, R. I., & Kim, Y. (2013) · Springer eBooks · doi:10.1007/978-1-4614-8317-5_12 · Cited by 1 · see citing works
Single-Cell Genomic and Epigenomic DNA Analyses
Geurs, S., Lefevre, T., & Voet, T. (2022) · Neuromethods · doi:10.1007/978-1-0716-2525-5_2 · Cited by 1 · see citing works
De la Cabalá y el mosaicismo somático en el sistema nervioso central
Kauffman, M. A. (2015) · Neurología Argentina · doi:10.1016/j.neuarg.2015.06.002
Buxbaum, E. (2015) · Springer eBooks · doi:10.1007/978-3-319-19920-7_10
THE CONTRIBUTION OF MOSAIC MUTATION TO AUTISM SPECTRUM DISORDER
Freed, D. N. (2017)
Perez-Maturo, J., Salinas, V., & Kauffman, M. A. (2020) · Elsevier eBooks · doi:10.1016/b978-0-12-817819-5.00005-x
The ubiquitin-proteasome system in neurodegenerative diseases
Verheijen, L. (2023) · doi:10.26481/dis.20231024lv
Morris, S. A. (2026) · Journal of Alzheimer s Disease Reports · doi:10.1177/25424823261472068
- Authors
- Beck, J. A.
- Affiliations
- MRC Prion Unit (GB)
- Corresponding author
- Beck, J. A.
- Venue
- Human Molecular Genetics
- Publisher
- Oxford University Press (OUP)
- Published
- 2004-04-28
- Volume
- 13
- Issue
- 12
- Pages
- 1219-1224
- ISSN
- 0964-6906 (ISSN-L)
- 1460-2083
- OpenAlex
- W2109880206
- Cited by
- 102
- References
- 19
- Citations by year
- 2026: 3 · 2025: 2 · 2024: 1 · 2023: 5 · 2022: 8 · 2021: 7 · 2020: 8 · 2019: 4 · 2018: 10 · 2017: 6 · 2016: 4 · 2015: 10 · 2014: 5 · 2013: 5 · 2012: 2
- FWCI
- 1.24
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Human Molecular Genetics (publishedVersion)
- PubMed (publishedVersion)
- UCL Discovery (University College London) (submittedVersion)
- HighWire Press Open Archive (submittedVersion)
- Funders
- Medical Research Council
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Neurology › Amyotrophic Lateral Sclerosis Research
- Keywords
- Alzheimer's disease, somatic mosaicism, germline mosaicism, presenilin 1, presenilin 2, amyloid precursor protein, somatic mutations, gene dosage effect, age of onset, cerebral cortex, lymphocytes
- MeSH terms
- Adult, Alzheimer Disease, Base Sequence, Female, Humans, Male, Membrane Proteins, Middle Aged, Mosaicism, Pedigree, Age of Onset, Germ-Line Mutation, Presenilin-1
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
