The neuropathology associated with repeat expansions in the C9ORF72 gene

Mackenzie, Ian R. A.; Frick, Petra; Neumann, Manuela

doi:10.1007/s00401-013-1232-4

Cited by 208Amyotrophic Lateral Sclerosis ResearchGenetic Neurodegenerative DiseasesAlzheimer's disease research and treatments

The neuropathology associated with repeat expansions in the C9ORF72 gene

Mackenzie, Ian R. A., Frick, Petra, Neumann, Manuela·2014·Acta Neuropathologica

DOI 10.1007/s00401-013-1232-4

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Abstract

An abnormal expansion of a GGGGCC hexanucleotide repeat in a non-coding region of the chromosome 9 open reading frame 72 gene (C9ORF72) is the most common genetic abnormality in familial and sporadic FTLD and ALS and the cause in most families where both, FTLD and ALS, are inherited. Pathologically, C9ORF72 expansion cases show a combination of FTLD-TDP and classical ALS with abnormal accumulation of TDP-43 into neuronal and oligodendroglial inclusions consistently seen in the frontal and temporal cortex, hippocampus and pyramidal motor system. In addition, a highly specific feature in C9ORF72 expansion cases is the presence of ubiquitin and p62 positive, but TDP-43 negative neuronal cytoplasmic and intranuclear inclusions. These TDP-43 negative inclusions contain dipeptide-repeat (DPR) proteins generated by unconventional repeat-associated translation of C9ORF72 transcripts with the expanded repeats and are most abundant in the cerebellum, hippocampus and all neocortex regions. Another consistent pathological feature associated with the production of C9ORF72 transcripts with expanded repeats is the formation of nuclear RNA foci that are frequently observed in the frontal cortex, hippocampus and cerebellum. Here, we summarize the complexity and heterogeneity of the neuropathology associated with the C9ORF72 expansion. We discuss implications of the data to the current classification of FTLD and critically review current insights from clinico-pathological correlative studies regarding the fundamental questions as to what processes are required and sufficient to trigger neurodegeneration in C9ORF72 disease pathogenesis.

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In C9orf72-related ALS and FTD, SQSTM1 accumulates together with ubiquitin in neurons and glia as well as muscle fibers.
“In the most commonly inherited form of ALS and FTD due to mutations in the C9orf72 gene (described below), SQSTM1 accumulates together with ubiquitin in neurons and glia [119–121] as well as muscle fibers [122].”
From Autophagy and ALS: mechanistic insights and therapeutic implications (2022) · cites this paper as [120]
ALS-FTD due to C9orf72 mutations displays TARDBP pathology, consisting of granular neuronal cytoplasmic inclusions, diffuse neuronal cytoplasmic staining, and glial cytoplasmic inclusions rich in TARDBP.
“ALS-FTD due to C9orf72 mutations displays TARDBP pathology, consisting of granular neuronal cytoplasmic inclusions, diffuse neuronal cytoplasmic staining, and glial cytoplasmic inclusions rich in TARDBP [120].”
From Autophagy and ALS: mechanistic insights and therapeutic implications (2022) · cites this paper as [120]

Ubiquitinated TDP-43 in Frontotemporal Lobar Degeneration and Amyotrophic Lateral Sclerosis
Neumann, M., Sampathu, D. M., Kwong, L. K., Truax, A. C., Micsenyi, M. C., Chou, T. T., Bruce, J., Schuck, T., Grossman, M., Clark, C. M., et al. (2006) · Science · doi:10.1126/science.1134108 · Cited by 6,576 · see citing works
Self-citation
Expanded GGGGCC Hexanucleotide Repeat in Noncoding Region of C9ORF72 Causes Chromosome 9p-Linked FTD and ALS
DeJesus-Hernandez, M., Mackenzie, I. R., Boeve, B. F., Boxer, A. L., Baker, M., Rutherford, N. J., Nicholson, A. M., Finch, N. A., Flynn, H., Adamson, J., et al. (2011) · Neuron · doi:10.1016/j.neuron.2011.09.011 · Cited by 4,936 · see citing works
Self-citation
A Hexanucleotide Repeat Expansion in C9ORF72 Is the Cause of Chromosome 9p21-Linked ALS-FTD
Renton, A. E., Majounie, E., Waite, A., Simón-Sánchez, J., Rollinson, S., Gibbs, J. R., Schymick, J. C., Laaksovirta, H., van Swieten, J. C., Myllykangas, L., et al. (2011) · Neuron · doi:10.1016/j.neuron.2011.09.010 · Cited by 4,409 · see citing works
The C9orf72 GGGGCC Repeat Is Translated into Aggregating Dipeptide-Repeat Proteins in FTLD/ALS
Mori, K., Weng, S., Arzberger, T., May, S., Rentzsch, K., Kremmer, E., Schmid, B., Kretzschmar, H. A., Cruts, M., Broeckhoven, C. V., et al. (2013) · Science · doi:10.1126/science.1232927 · Cited by 1,248 · see citing works
Unconventional Translation of C9ORF72 GGGGCC Expansion Generates Insoluble Polypeptides Specific to c9FTD/ALS
Ash, P. E. A., Bieniek, K. F., Gendron, T. F., Caulfield, T. R., Lin, W.-L., DeJesus‐Hernandez, M., van Blitterswijk, M., Jansen‐West, K. R., Paul, J. W., Rademakers, R., et al. (2013) · Neuron · doi:10.1016/j.neuron.2013.02.004 · Cited by 1,079 · see citing works
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Mackenzie, I. R., Neumann, M., Baborie, A., Sampathu, D. M., du Plessis, D., Jaros, E., Perry, R. H., Trojanowski, J. Q., Mann, D. M. A., & Lee, V. M. ‐. (2011) · Acta Neuropathologica · doi:10.1007/s00401-011-0845-8 · Cited by 1,013 · see citing works
Self-citation
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Mackenzie, I. R. A., Neumann, M., Bigio, E. H., Cairns, N. J., Alafuzoff, I., Kril, J., Kovacs, G. G., Ghetti, B., Halliday, G., Holm, I. E., et al. (2010) · Acta Neuropathologica · doi:10.1007/s00401-009-0612-2 · Cited by 1,012 · see citing works
Self-citation
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Mackenzie, I. R. A., Bigio, E. H., Ince, P. G., Geser, F., Neumann, M., Cairns, N. J., Kwong, L. K., Forman, M. S., Ravits, J., Stewart, H., et al. (2007) · Annals of Neurology · doi:10.1002/ana.21147 · Cited by 992 · see citing works
Self-citation
TDP-43 and FUS in amyotrophic lateral sclerosis and frontotemporal dementia
Mackenzie, I. R., Rademakers, R., & Neumann, M. (2010) · The Lancet Neurology · doi:10.1016/s1474-4422(10)70195-2 · Cited by 977 · see citing works
Self-citation
Non-ATG–initiated translation directed by microsatellite expansions
Zu, T., Gibbens, B. B., Doty, N. S., Gomes-Pereira, M., Huguet-Lachon, A., Stone, M. D., Margolis, J., Peterson, M., Markowski, T. W., Ingram, M. A. C., et al. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1013343108 · Cited by 904 · see citing works
RNA Toxicity from the ALS/FTD C9ORF72 Expansion Is Mitigated by Antisense Intervention
Donnelly, C. J., Zhang, P.-W., Pham, J. T., Haeusler, A. R., Mistry, N. A., Vidensky, S., Daley, E. L., Poth, E. M., Hoover, B., Fines, D. M., et al. (2013) · Neuron · doi:10.1016/j.neuron.2013.10.015 · Cited by 877 · see citing works
Prevalence and patterns of cognitive impairment in sporadic ALS
Ringholz, G. M., Appel, S. H., Bradshaw, M. R., Cooke, N., Mosnik, D. M., & Schulz, P. E. (2005) · Neurology · doi:10.1212/01.wnl.0000172911.39167.b6 · Cited by 843 · see citing works
The overlap of amyotrophic lateral sclerosis and frontotemporal dementia
Lomen, C. E., Anderson, T. T., & Miller, B. L. (2002) · Neurology · doi:10.1212/wnl.59.7.1077 · Cited by 699 · see citing works
Gains or losses: molecular mechanisms of TDP43-mediated neurodegeneration
Lee, E. B., Lee, V. M.-Y., & Trojanowski, J. Q. (2012) · Nature Reviews Neuroscience · doi:10.1038/nrn3121 · Cited by 659 · see citing works
A C9orf72 promoter repeat expansion in a Flanders-Belgian cohort with disorders of the frontotemporal lobar degeneration-amyotrophic lateral sclerosis spectrum: a gene identification study
Gijselinck, I., Langenhove, T. V., van der Zee, J., Sleegers, K., Philtjens, S., Kleinberger, G., Janssens, J., Bettens, K., Cauwenberghe, C. V., Pereson, S., et al. (2011) · The Lancet Neurology · doi:10.1016/s1474-4422(11)70261-7 · Cited by 635 · see citing works
Are amyotrophic lateral sclerosis patients cognitively normal?
Lomen-Hoerth, C., Murphy, J. M., Langmore, S. E., Kramer, J. H., Olney, R. K., & Miller, B. L. (2003) · Neurology · doi:10.1212/01.wnl.0000055861.95202.8d · Cited by 616 · see citing works
Phosphorylation of S409/410 of TDP-43 is a consistent feature in all sporadic and familial forms of TDP-43 proteinopathies
Neumann, M., Kwong, L. K., Lee, E. B., Kremmer, E., Flatley, A., Xu, Y., Forman, M. S., Troost, D., Kretzschmar, H. A., Trojanowski, J. Q., et al. (2009) · Acta Neuropathologica · doi:10.1007/s00401-008-0477-9 · Cited by 604 · see citing works
Self-citation
Antisense transcripts of the expanded C9ORF72 hexanucleotide repeat form nuclear RNA foci and undergo repeat-associated non-ATG translation in c9FTD/ALS
Gendron, T. F., Bieniek, K. F., Zhang, Y., Jansen‐West, K. R., Ash, P. E. A., Caulfield, T. R., Daughrity, L. M., Dunmore, J., Castanedes‐Casey, M., Chew, J., et al. (2013) · Acta Neuropathologica · doi:10.1007/s00401-013-1192-8 · Cited by 569 · see citing works
Targeted degradation of sense and antisense C9orf72 RNA foci as therapy for ALS and frontotemporal degeneration
Lagier‐Tourenne, C., Baughn, M. W., Rigo, F., Sun, S., Liu, P., Li, H., Jiang, J., Watt, A. T., Chun, S. J., Katz, M., et al. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1318835110 · Cited by 555 · see citing works
TDP-43 in Familial and Sporadic Frontotemporal Lobar Degeneration with Ubiquitin Inclusions
Cairns, N. J., Neumann, M., Bigio, E. H., Holm, I. E., Troost, D., Hatanpaa, K. J., Foong, C., White, C. L., Schneider, J. A., Kretzschmar, H. A., et al. (2007) · American Journal Of Pathology · doi:10.2353/ajpath.2007.070182 · Cited by 535 · see citing works
Self-citation
Distinct clinical and pathological characteristics of frontotemporal dementia associated with C9ORF72 mutations
Snowden, J. S., Rollinson, S., Thompson, J. C., Harris, J. M., Stopford, C. L., Richardson, A. M. T., Jones, M., Gerhard, A., Davidson, Y. S., Robinson, A., et al. (2012) · Brain · doi:10.1093/brain/awr355 · Cited by 523 · see citing works
Hexanucleotide Repeats in ALS/FTD Form Length-Dependent RNA Foci, Sequester RNA Binding Proteins, and Are Neurotoxic
Lee, Y., Chen, H.-J., Peres, J., Gómez-Deza, J., Attig, J., Štalekar, M., Troakes, C., Nishimura, A. L., Scotter, E. L., Vance, C. A., et al. (2013) · Cell Reports · doi:10.1016/j.celrep.2013.10.049 · Cited by 487 · see citing works
Bidirectional transcripts of the expanded C9orf72 hexanucleotide repeat are translated into aggregating dipeptide repeat proteins
Mori, K., Arzberger, T., Grässer, F. A., Gijselinck, I., May, S., Rentzsch, K., Weng, S., Schludi, M. H., van der Zee, J., Cruts, M., et al. (2013) · Acta Neuropathologica · doi:10.1007/s00401-013-1189-3 · Cited by 482 · see citing works
p62 positive, TDP-43 negative, neuronal cytoplasmic and intranuclear inclusions in the cerebellum and hippocampus define the pathology of C9orf72-linked FTLD and MND/ALS
Al-Sarraj, S., King, A., Troakes, C., Smith, B., Maekawa, S., Bodi, I., Rogelj, B., Al-Chalabi, A., Hortobágyi, T., & Shaw, C. E. (2011) · Acta Neuropathologica · doi:10.1007/s00401-011-0911-2 · Cited by 475 · see citing works
Frontotemporal dementia with the C9ORF72 hexanucleotide repeat expansion: clinical, neuroanatomical and neuropathological features
Mahoney, C., Beck, J. A., Rohrer, J. D., Lashley, T., Mok, K. Y., Shakespeare, T. J., Yeatman, T., Warrington, E. K., Schott, J. M., Fox, N. C., et al. (2012) · Brain · doi:10.1093/brain/awr361 · Cited by 431 · see citing works
Bidirectional expression of CUG and CAG expansion transcripts and intranuclear polyglutamine inclusions in spinocerebellar ataxia type 8
Moseley, M. L., Zu, T., Ikeda, Y., Gao, W., Mosemiller, A. K., Daughters, R. S., Chen, G., Weatherspoon, M. R., Clark, H. B., Ebner, T. J., et al. (2006) · Nature Genetics · doi:10.1038/ng1827 · Cited by 422 · see citing works
Nomenclature for neuropathologic subtypes of frontotemporal lobar degeneration: consensus recommendations
Mackenzie, I. R., Neumann, M., Bigio, E. H., Cairns, N. J., Alafuzoff, I. I., Kril, J. J., Kovács, G. G., Ghetti, B. F., Halliday, G. M., Holm, I. E., et al. (2008) · Acta Neuropathologica · doi:10.1007/s00401-008-0460-5 · Cited by 418 · see citing works
Self-citation
Advances in understanding the molecular basis of frontotemporal dementia
Rademakers, R., Neumann, M., & Mackenzie, I. R. (2012) · Nature Reviews Neurology · doi:10.1038/nrneurol.2012.117 · Cited by 414 · see citing works
Self-citation
Concomitant TAR-DNA-Binding Protein 43 Pathology Is Present in Alzheimer Disease and Corticobasal Degeneration but Not in Other Tauopathies
Uryu, K., Nakashima-Yasuda, H., Forman, M. S., Kwong, L. K., Clark, C. M., Grossman, M., Miller, B. L., Kretzschmar, H. A., Lee, V. M.-Y., Trojanowski, J. Q., et al. (2008) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/nen.0b013e31817713b5 · Cited by 382 · see citing works
Self-citation
Understanding the role of TDP-43 and FUS/TLS in ALS and beyond
Da Cruz, S., & Cleveland, D. W. (2011) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2011.05.029 · Cited by 351 · see citing works
Phosphorylated TDP-43 in Alzheimer’s disease and dementia with Lewy bodies
Arai, T., Mackenzie, I. R. A., Hasegawa, M., Nonoka, T., Niizato, K., Tsuchiya, K., Iritani, S., Onaya, M., & Akiyama, H. (2009) · Acta Neuropathologica · doi:10.1007/s00401-008-0480-1 · Cited by 345 · see citing works
Self-citation
Dipeptide repeat protein pathology in C9ORF72 mutation cases: clinico-pathological correlations
Mackenzie, I. R., Arzberger, T., Kremmer, E., Troost, D., Lorenzl, S., Mori, K., Weng, S.-M., Haass, C., Kretzschmar, H. A., Edbauer, D., et al. (2013) · Acta Neuropathologica · doi:10.1007/s00401-013-1181-y · Cited by 345 · see citing works
Self-citation
Characterization of frontotemporal dementia and/or amyotrophic lateral sclerosis associated with the GGGGCC repeat expansion in C9ORF72
Boeve, B. F., Boylan, K., Graff‐Radford, N. R., DeJesus‐Hernandez, M., Knopman, D. S., Pedraza, O., Vemuri, P., Jones, D. T., Lowe, V. J., Murray, M. E., et al. (2012) · Brain · doi:10.1093/brain/aws004 · Cited by 344 · see citing works
hnRNP A3 binds to GGGGCC repeats and is a constituent of p62-positive/TDP43-negative inclusions in the hippocampus of patients with C9orf72 mutations
Mori, K., Lammich, S., Mackenzie, I. R., Forné, I., Zilow, S., Kretzschmar, H. A., Edbauer, D., Janssens, J., Kleinberger, G., Cruts, M., et al. (2013) · Acta Neuropathologica · doi:10.1007/s00401-013-1088-7 · Cited by 339 · see citing works
Self-citation
Motor Neuron dysfunction in frontotemporal dementia
Burrell, J. R., Kiernan, M. C., Vucic, S., & Hodges, J. R. (2011) · Brain · doi:10.1093/brain/awr195 · Cited by 339 · see citing works
Expanded GGGGCC repeat RNA associated with amyotrophic lateral sclerosis and frontotemporal dementia causes neurodegeneration
Xu, Z., Poidevin, M., Li, X., Li, Y., Shu, L., Nelson, D. L., Li, H., Hales, C. M., Gearing, M., Wingo, T. S., et al. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1219643110 · Cited by 334 · see citing works
Loss of function of C9orf72 causes motor deficits in a zebrafish model of amyotrophic lateral sclerosis
Ciura, S., Lattante, S., Le Ber, I., Latouche, M., Tostivint, H., Brice, A., & Kabashi, E. (2013) · Annals of Neurology · doi:10.1002/ana.23946 · Cited by 333 · see citing works
Clinico-pathological features in amyotrophic lateral sclerosis with expansions in C9ORF72
Cooper‐Knock, J., Hewitt, C., Highley, J. R., Brockington, A., Milano, A., Man, S., Martindale, J. E., Hartley, J. A., Walsh, T., Gelsthorpe, C., et al. (2012) · Brain · doi:10.1093/brain/awr365 · Cited by 329 · see citing works
TDP-43 in the Ubiquitin Pathology of Frontotemporal Dementia With VCP Gene Mutations
Neumann, M., Mackenzie, I. R., Cairns, N. J., Boyer, P. J., Markesbery, W. R., Smith, C. D., Taylor, J. P., Kretzschmar, H. A., Kimonis, V. E., & Forman, M. S. (2007) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/nen.0b013e31803020b9 · Cited by 326 · see citing works
Self-citation
Heterogeneity of ubiquitin pathology in frontotemporal lobar degeneration: classification and relation to clinical phenotype
Mackenzie, I. R., Baborie, A., Pickering-Brown, S. M., du Plessis, D., Jaros, E., Perry, R. H., Neary, D., Snowden, J. S., & Mann, D. M. A. (2006) · Acta Neuropathologica · doi:10.1007/s00401-006-0138-9 · Cited by 322 · see citing works
Self-citation
Modeling key pathological features of frontotemporal dementia with C9ORF72 repeat expansion in iPSC-derived human neurons
Almeida, S., Gascon, E., Tran, H., Chou, H. J., Gendron, T. F., DeGroot, S., Tapper, A. R., Sellier, C., Charlet-Berguerand, N., Karydas, A., et al. (2013) · Acta Neuropathologica · doi:10.1007/s00401-013-1149-y · Cited by 321 · see citing works
C9orf72 frontotemporal lobar degeneration is characterised by frequent neuronal sense and antisense RNA foci
Mizielinska, S., Lashley, T., Norona, F. E., Clayton, E. L., Ridler, C. E., Fratta, P., & Isaacs, A. M. (2013) · Acta Neuropathologica · doi:10.1007/s00401-013-1200-z · Cited by 317 · see citing works
Pathological Heterogeneity of Frontotemporal Lobar Degeneration with Ubiquitin-Positive Inclusions Delineated by Ubiquitin Immunohistochemistry and Novel Monoclonal Antibodies
Sampathu, D. M., Neumann, M., Kwong, L. K., Chou, T. T. T., Micsenyi, M. C., Truax, A. C., BRUCE, J. S., Grossman, M., Trojanowski, J. Q., & Lee, V. M. ‐. (2006) · American Journal Of Pathology · doi:10.2353/ajpath.2006.060438 · Cited by 317 · see citing works
Self-citation
Reduced C9orf72 gene expression in c9FTD/ALS is caused by histone trimethylation, an epigenetic event detectable in blood
Belzil, V., Bauer, P., Prudencio, M., Gendron, T. F., Stetler, C. T., Yan, I. K., Pregent, L., Daughrity, L. M., Baker, M., Rademakers, R., et al. (2013) · Acta Neuropathologica · doi:10.1007/s00401-013-1199-1 · Cited by 309 · see citing works
Ubiquitinated pathological lesions in frontotemporal lobar degeneration contain the TAR DNA-binding protein, TDP-43
Davidson, Y. S., Kelley, T., Mackenzie, I. R., Pickering-Brown, S. M., du Plessis, D., Neary, D., Snowden, J. S., & Mann, D. M. A. (2007) · Acta Neuropathologica · doi:10.1007/s00401-006-0189-y · Cited by 299 · see citing works
Self-citation
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Murray, M. E., DeJesus‐Hernandez, M., Rutherford, N. J., Baker, M. C., Duara, R., Graff‐Radford, N. R., Wszołek, Z. K., Ferman, T. J., Josephs, K. A., Boylan, K., et al. (2011) · Acta Neuropathologica · doi:10.1007/s00401-011-0907-y · Cited by 295 · see citing works
The neuropathology of frontotemporal lobar degeneration caused by mutations in the progranulin gene
Mackenzie, I. R., Baker, M., Pickering-Brown, S. M., Hsiung, G. R., Lindholm, C., Dwosh, E., Gass, J. M., Cannon, A. D., Rademakers, R., Hutton, M., et al. (2006) · Brain · doi:10.1093/brain/awl271 · Cited by 294 · see citing works
Self-citation
The multiple roles of TDP-43 in pre-mRNA processing and gene expression regulation
Buratti, E., & Baralle, F. E. (2010) · RNA Biology · doi:10.4161/rna.7.4.12205 · Cited by 284 · see citing works
Hypermethylation of the CpG Island Near the G4C2 Repeat in ALS with a C9orf72 Expansion
Xi, Z., Zinman, L. H., Moreno, D., Schymick, J. C., Liang, Y., Sato, C., Zheng, Y., Ghani, M., Dib, S., Keith, J. L., et al. (2013) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2013.04.017 · Cited by 267 · see citing works
The clinical and pathological phenotype of C9ORF72 hexanucleotide repeat expansions
Simón‐Sánchez, J., Dopper, E. G. P., Cohn‐Hokke, P. E., Hukema, R. K., Nicolaou, N., Seelaar, H., de Graaf, J. R. A., de Koning, I., van Schoor, N. M., Deeg, D. J. H., et al. (2012) · Brain · doi:10.1093/brain/awr353 · Cited by 266 · see citing works
Cellular toxicity of expanded RNA repeats: focus on RNA foci
Wojciechowska, M., & Krzyżosiak, W. J. (2011) · Human Molecular Genetics · doi:10.1093/hmg/ddr299 · Cited by 235 · see citing works
Clinical and pathological features of familial frontotemporal dementia caused by C9ORF72 mutation on chromosome 9p
Hsiung, G. R., DeJesus-Hernandez, M., Feldman, H., Sengdy, P., Bouchard‐Kerr, P., Dwosh, E., Butler, R. K., Leung, B., Fok, A., Rutherford, N. J., et al. (2012) · Brain · doi:10.1093/brain/awr354 · Cited by 220 · see citing works
Self-citation
How do C9ORF72 repeat expansions cause amyotrophic lateral sclerosis and frontotemporal dementia
van Blitterswijk, M., DeJesus‐Hernandez, M., & Rademakers, R. (2012) · Current Opinion in Neurology · doi:10.1097/wco.0b013e32835a3efb · Cited by 200 · see citing works
Clinical, neuroimaging and neuropathological features of a new chromosome 9p-linked FTD-ALS family
Boxer, A. L., Mackenzie, I. R., Boeve, B. F., Baker, M., Seeley, W. W., Crook, R., Feldman, H., Hsiung, G. R., Rutherford, N. J., Laluz, V., et al. (2010) · Journal of Neurology Neurosurgery & Psychiatry · doi:10.1136/jnnp.2009.204081 · Cited by 194 · see citing works
Self-citation
Pattern of ubiquilin pathology in ALS and FTLD indicates presence of C9ORF72 hexanucleotide expansion
Brettschneider, J., Deerlin, V. M. V., Robinson, J. L., Kwong, L. K., Lee, E. B., Ali, Y., Safren, N., Monteiro, M. J., Toledo, J. B., Elman, L. B., et al. (2012) · Acta Neuropathologica · doi:10.1007/s00401-012-0970-z · Cited by 183 · see citing works
Dipeptide repeat proteins are present in the p62 positive inclusions in patients with frontotemporal lobar degeneration and motor neurone disease associated with expansions in C9ORF72
Mann, D. M., Rollinson, S., Robinson, A., Bennion Callister, J., Thompson, J. C., Snowden, J. S., Gendron, T., Petrucelli, L., Masuda-Suzukake, M., Hasegawa, M., et al. (2013) · Acta Neuropathologica Communications · doi:10.1186/2051-5960-1-68 · Cited by 182 · see citing works
Clinical and pathological features of amyotrophic lateral sclerosis caused by mutation in the C9ORF72 gene on chromosome 9p
Stewart, H. G., Rutherford, N. J., Briemberg, H., Krieger, C., Cashman, N. R., Fabros, M., Baker, M. C., Fok, A., DeJesus‐Hernandez, M., Eisen, A., et al. (2012) · Acta Neuropathologica · doi:10.1007/s00401-011-0937-5 · Cited by 156 · see citing works
Self-citation
Repeat-associated non-ATG (RAN) translation in neurological disease
Cleary, J. D., & Ranum, L. P. W. (2013) · Human Molecular Genetics · doi:10.1093/hmg/ddt371 · Cited by 143 · see citing works
Amyloid deposits: Protection against toxic protein species?
Treusch, S., Cyr, D., & Lindquist, S. L. (2009) · Cell Cycle · doi:10.4161/cc.8.11.8503 · Cited by 134 · see citing works
An MND/ALS phenotype associated with C9orf72 repeat expansion: Abundant p62‐positive, TDP‐43‐negative inclusions in cerebral cortex, hippocampus and cerebellum but without associated cognitive decline
Troakes, C., Maekawa, S., Wijesekera, L., Rogelj, B., Siklós, L., Bell, C., Smith, B., Newhouse, S., Vance, C., Johnson, L., et al. (2012) · Neuropathology · doi:10.1111/j.1440-1789.2011.01286.x · Cited by 124 · see citing works
Common Variant in GRN Is a Genetic Risk Factor for Hippocampal Sclerosis in the Elderly
Dickson, D. W., Baker, M., & Rademakers, R. (2010) · Neurodegenerative Diseases · doi:10.1159/000289231 · Cited by 100 · see citing works
Mechanisms of disease in frontotemporal lobar degeneration: gain of function versus loss of function effects
Halliday, G. M., Bigio, E. H., Cairns, N. J., Neumann, M., Mackenzie, I. R., & Mann, D. M. A. (2012) · Acta Neuropathologica · doi:10.1007/s00401-012-1030-4 · Cited by 98 · see citing works
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Tau pathology in frontotemporal lobar degeneration with C9ORF72 hexanucleotide repeat expansion
Bieniek, K. F., Murray, M. E., Rutherford, N. J., Castanedes‐Casey, M., DeJesus‐Hernandez, M., Liesinger, A. M., Baker, M., Boylan, K., Rademakers, R., & Dickson, D. W. (2012) · Acta Neuropathologica · doi:10.1007/s00401-012-1048-7 · Cited by 94 · see citing works
Pedigree with frontotemporal lobar degeneration – motor neuron disease and Tar DNA binding protein-43 positive neuropathology: genetic linkage to chromosome 9
Luty, A. A., Kwok, J. B., Thompson, E. M., Blumbergs, P. C., Brooks, W. S., Loy, C. T., Dobson‐Stone, C., Panegyres, P. K., Hecker, J. R., Nicholson, G. A., et al. (2008) · BMC Neurology · doi:10.1186/1471-2377-8-32 · Cited by 86 · see citing works
RNA-mediated toxicity in neurodegenerative disease
Belzil, V., Gendron, T. F., & Petrucelli, L. (2012) · Molecular and Cellular Neuroscience · doi:10.1016/j.mcn.2012.12.006 · Cited by 86 · see citing works
Familial frontotemporal dementia with amyotrophic lateral sclerosis and a shared haplotype on chromosome 9p
Pearson, J. P., Williams, N. M., Majounie, E., Waite, A., Stott, J., Newsway, V., Murray, A., Hernandez, D., Guerreiro, R., Singleton, A. B., et al. (2011) · Journal of Neurology · doi:10.1007/s00415-010-5815-x · Cited by 84 · see citing works
Neuropathologic Features of Frontotemporal Lobar Degeneration With Ubiquitin-Positive Inclusions Visualized With Ubiquitin-Binding Protein p62 Immunohistochemistry
Pikkarainen, M., Hartikainen, P. H., & Alafuzoff, I. I. (2008) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/nen.0b013e31816a1da2 · Cited by 82 · see citing works
Identification of 2 Loci at Chromosomes 9 and 14 in a Multiplex Family With Frontotemporal Lobar Degeneration and Amyotrophic Lateral Sclerosis
Gijselinck, I., Engelborghs, S., Maes, G., Cuijt, I., Peeters, K., Mattheijssens, M., Joris, G., Cras, P. P., Martin, J., Deyn, P. P. D., et al. (2010) · Archives of Neurology · doi:10.1001/archneurol.2010.82 · Cited by 55 · see citing works
Corticospinal tract degeneration associated with TDP-43 type C pathology and semantic dementia
Josephs, K. A., Whitwell, J. L., Murray, M. E., Parisi, J. E., Graff‐Radford, N. R., Knopman, D. S., Boeve, B. F., Senjem, M. L., Rademakers, R., Jack, C. R., et al. (2013) · Brain · doi:10.1093/brain/aws324 · Cited by 47 · see citing works

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The cerebellum and cognition
Schmahmann, J. D. (2019) · Neuroscience Letters · doi:10.1016/j.neulet.2018.07.005 · Cited by 1,625 · see citing works
Frontotemporal dementia
Bang, J., Spina, S., & Miller, B. L. (2015) · The Lancet · doi:10.1016/s0140-6736(15)00461-4 · Cited by 1,144 · see citing works
Gain of toxicity from ALS/FTD-linked repeat expansions in C9ORF72 is alleviated by antisense oligonucleotides targeting GGGGCC-containing RNAs
Jiang, J., Zhu, Q., Gendron, T. F., Saberi, S., McAlonis-Downes, M., Seelman, A., Stauffer, J. E., Jafar-nejad, P., Drenner, K., Schulte, D., et al. (2016) · Neuron · doi:10.1016/j.neuron.2016.04.006 · Cited by 536 · see citing works
Extracellular vesicles in neurodegenerative disease — pathogenesis to biomarkers
Thompson, A. G., Gray, E., Heman-Ackah, S. M., Mäger, I., Talbot, K., Andaloussi, S. E., Wood, M. J., & Turner, M. R. (2016) · Nature Reviews Neurology · doi:10.1038/nrneurol.2016.68 · Cited by 431 · see citing works
C9ORF72 repeat expansions in mice cause TDP-43 pathology, neuronal loss, and behavioral deficits
Chew, J., Gendron, T. F., Prudencio, M., Sasaguri, H., Zhang, Y., Castanedes‐Casey, M., Lee, C. W., Jansen‐West, K. R., Kurti, A., Murray, M. E., et al. (2015) · Science · doi:10.1126/science.aaa9344 · Cited by 410 · see citing works
The C9orf72 protein interacts with Rab1a and the ULK1 complex to regulate initiation of autophagy
Webster, C. P., Smith, E. F., Bauer, C. S., Moller, A., Hautbergue, G. M., Ferraiuolo, L., Myszczynska, M. A., Higginbottom, A., Walsh, M. J., Whitworth, A. J., et al. (2016) · The EMBO Journal · doi:10.15252/embj.201694401 · Cited by 404 · see citing works
The frontotemporal dementia-motor neuron disease continuum
Burrell, J. R., Halliday, G. M., Kril, J. J., Ittner, L. M., Götz, J., Kiernan, M. C., & Hodges, J. R. (2016) · The Lancet · doi:10.1016/s0140-6736(16)00737-6 · Cited by 369 · see citing works
The cerebellum in Alzheimer’s disease: evaluating its role in cognitive decline
Jacobs, H. I. L., Hopkins, D. A., Mayrhofer, H. C., Bruner, E., van Leeuwen, F. W., Raaijmakers, W., & Schmahmann, J. D. (2017) · Brain · doi:10.1093/brain/awx194 · Cited by 339 · see citing works
Molecular Pathological Classification of Neurodegenerative Diseases: Turning towards Precision Medicine
Kovács, G. G. (2016) · International Journal of Molecular Sciences · doi:10.3390/ijms17020189 · Cited by 321 · see citing works
Drosophila as an In Vivo Model for Human Neurodegenerative Disease
McGurk, L., Berson, A., & Bonini, N. M. (2015) · Genetics · doi:10.1534/genetics.115.179457 · Cited by 314 · see citing works
Neuropathology of amyotrophic lateral sclerosis and its variants
Saberi, S., Stauffer, J. E., Schulte, D. J., & Ravits, J. (2015) · Neurologic Clinics · doi:10.1016/j.ncl.2015.07.012 · Cited by 282 · see citing works
Molecular pathology of neurodegenerative diseases: principles and practice
Kovács, G. G. (2019) · Journal of Clinical Pathology · doi:10.1136/jclinpath-2019-205952 · Cited by 243 · see citing works
Quantitative analysis and clinico-pathological correlations of different dipeptide repeat protein pathologies in C9ORF72 mutation carriers
Mackenzie, I. R. A., Frick, P., Grässer, F. A., Gendron, T. F., Petrucelli, L., Cashman, N. R., Edbauer, D., Kremmer, E., Prudlo, J., Troost, D., et al. (2015) · Acta Neuropathologica · doi:10.1007/s00401-015-1476-2 · Cited by 231 · see citing works
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CRISPR–Cas9 screens in human cells and primary neurons identify modifiers of C9ORF72 dipeptide-repeat-protein toxicity
Kramer, N. J., Haney, M. S., Morgens, D. W., Jovičić, A., Couthouis, J., Li, A., Ousey, J., Ma, R., Bieri, G., Tsui, C. K., et al. (2018) · Nature Genetics · doi:10.1038/s41588-018-0070-7 · Cited by 226 · see citing works
Sporadic and hereditary amyotrophic lateral sclerosis (ALS)
Ajroud‐Driss, S., & Siddique, T. (2014) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2014.08.010 · Cited by 205 · see citing works
Autophagy and ALS: mechanistic insights and therapeutic implications
Chua, J. P., De Calbiac, H., Kabashi, E., & Barmada, S. J. (2022) · Autophagy · doi:10.1080/15548627.2021.1926656 · Cited by 189 · see citing works
“fuse neuronal cytoplasmic staining, and glial cytoplasmic inclusions rich in TARDBP [120].”
Background
Human ALS/FTD brain organoid slice cultures display distinct early astrocyte and targetable neuronal pathology
Szebényi, K., Wenger, L. M. D., Sun, Y., Dunn, A. W., Limegrover, C. A., Gibbons, G. M., Conci, E., Paulsen, O., Mierau, S. B., Balmus, G., et al. (2021) · Nature Neuroscience · doi:10.1038/s41593-021-00923-4 · Cited by 181 · see citing works
C9orf72 hypermethylation protects against repeat expansion-associated pathology in ALS/FTD
Liu, E. Y., Russ, J., Wu, K., Neal, D., Suh, E., McNally, A. G., Irwin, D. J., Van Deerlin, V. M., & Lee, E. B. (2014) · Acta Neuropathologica · doi:10.1007/s00401-014-1286-y · Cited by 180 · see citing works
Antisense RNA foci in the motor neurons of C9ORF72-ALS patients are associated with TDP-43 proteinopathy
Cooper‐Knock, J., Higginbottom, A., Stopford, M. J., Highley, J. R., Ince, P. G., Wharton, S. B., Pickering-Brown, S. M., Kirby, J., Hautbergue, G. M., & Shaw, P. J. (2015) · Acta Neuropathologica · doi:10.1007/s00401-015-1429-9 · Cited by 175 · see citing works
LATE-NC staging in routine neuropathologic diagnosis: an update
Nelson, P. T., Lee, E. B., Cykowski, M. D., Alafuzoff, I. I., Arfanakis, K., Attems, J., Brayne, C., Corrada, M. M., Dugger, B. N., Flanagan, M. E., et al. (2022) · Acta Neuropathologica · doi:10.1007/s00401-022-02524-2 · Cited by 175 · see citing works
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C9ORF72: What It Is, What It Does, and Why It Matters
Smeyers, J., Banchi, E.-G., & Latouche, M. (2021) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2021.661447 · Cited by 175 · see citing works
RNA toxicity in non‐coding repeat expansion disorders
Swinnen, B., Robberecht, W., & Bosch, L. V. D. (2019) · The EMBO Journal · doi:10.15252/embj.2018101112 · Cited by 163 · see citing works
Disrupted neuronal trafficking in amyotrophic lateral sclerosis
Burk, K., & Pasterkamp, R. J. (2019) · Acta Neuropathologica · doi:10.1007/s00401-019-01964-7 · Cited by 162 · see citing works
Aberrant deposition of stress granule-resident proteins linked to C9orf72-associated TDP-43 proteinopathy
Chew, J., Cook, C. N., Gendron, T. F., Jansen‐West, K. R., del Rosso, G., Daughrity, L. M., Castanedes‐Casey, M., Kurti, A., Stankowski, J. N., Disney, M. D., et al. (2019) · Molecular Neurodegeneration · doi:10.1186/s13024-019-0310-z · Cited by 158 · see citing works
Mechanisms of FUS mutations in familial amyotrophic lateral sclerosis
Shang, Y., & Huang, E. J. (2016) · Brain Research · doi:10.1016/j.brainres.2016.03.036 · Cited by 154 · see citing works
There has been an awakening: Emerging mechanisms of C9orf72 mutations in FTD/ALS
Gitler, A. D., & Tsuiji, H. (2016) · Brain Research · doi:10.1016/j.brainres.2016.04.004 · Cited by 152 · see citing works
Autophagy Dysregulation in ALS: When Protein Aggregates Get Out of Hand
Ramesh, N., & Pandey, U. B. (2017) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2017.00263 · Cited by 150 · see citing works
Early Cognitive, Structural, and Microstructural Changes in Presymptomatic C9orf72 Carriers Younger Than 40 Years
Bertrand, A., Wen, J., Rinaldi, D., Houot, M., Sayah, S., Camuzat, A., Fournier, C., Fontanella, S., Routier, A., Couratier, P., et al. (2018) · JAMA Neurology · doi:10.1001/jamaneurol.2017.4266 · Cited by 146 · see citing works
Isoform‐specific antibodies reveal distinct subcellular localizations of C 9orf72 in amyotrophic lateral sclerosis
Xiao, S., MacNair, L., McGoldrick, P., McKeever, P. M., McLean, J. R., Zhang, M., Keith, J. L., Zinman, L. H., Rogaeva, E. A., & Robertson, J. (2015) · Annals of Neurology · doi:10.1002/ana.24469 · Cited by 139 · see citing works
Ubiquitin pathways in neurodegenerative disease
Atkin, G., & Paulson, H. L. (2014) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2014.00063 · Cited by 136 · see citing works
C9orf72 arginine-rich dipeptide repeat proteins disrupt karyopherin-mediated nuclear import
Hayes, L. R., Duan, L., Bowen, K., Kaláb, P., & Rothstein, J. D. (2020) · eLife · doi:10.7554/elife.51685 · Cited by 133 · see citing works
The basis of clinicopathological heterogeneity in TDP-43 proteinopathy
Kawakami, I., Arai, T., & Hasegawa, M. (2019) · Acta Neuropathologica · doi:10.1007/s00401-019-02077-x · Cited by 128 · see citing works
Genetic Convergence Brings Clarity to the Enigmatic Red Line in ALS
Cook, C. N., & Petrucelli, L. (2019) · Neuron · doi:10.1016/j.neuron.2019.02.032 · Cited by 124 · see citing works
Basal ganglia pathology in ALS is associated with neuropsychological deficits
Machts, J., Loewe, K., Kaufmann, J., Jakubiczka, S., Abdulla, S., Petri, S., Dengler, R., Heinze, H., Vielhaber, S., Schoenfeld, M. A., et al. (2015) · Neurology · doi:10.1212/wnl.0000000000002017 · Cited by 124 · see citing works
Translation of dipeptide repeat proteins from the C9ORF72 expanded repeat is associated with cellular stress
Sonobe, Y., Ghadge, G. D., Masaki, K., Sendoel, A., Fuchs, E. V., & Roos, R. P. (2018) · Neurobiology of Disease · doi:10.1016/j.nbd.2018.05.009 · Cited by 111 · see citing works
Longitudinal structural changes in ALS: a three time-point imaging study of white and gray matter degeneration
Bede, P., & Hardiman, O. M. (2017) · Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration · doi:10.1080/21678421.2017.1407795 · Cited by 109 · see citing works
Disease Mechanisms ofC9ORF72Repeat ExpansionsPreprint
Gendron, T. F., & Petrucelli, L. (2017) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a024224 · Cited by 101 · see citing works
Protein Homeostasis in Amyotrophic Lateral Sclerosis: Therapeutic Opportunities?
Webster, C. P., Smith, E. F., Shaw, P. J., & Vos, K. J. D. (2017) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2017.00123 · Cited by 99 · see citing works
Repeat-associated non-ATG (RAN) translation
Cleary, J. D., Pattamatta, A., & Ranum, L. P. W. (2018) · Journal of Biological Chemistry · doi:10.1074/jbc.r118.003237 · Cited by 95 · see citing works
Dipeptide repeat protein inclusions are rare in the spinal cord and almost absent from motor neurons in C9ORF72 mutant amyotrophic lateral sclerosis and are unlikely to cause their degeneration
Gomez-Deza, J., Lee, Y.-B., Troakes, C., Nolan, M., Al-Sarraj, S., Gallo, J.-M., & Shaw, C. E. (2015) · Acta Neuropathologica Communications · doi:10.1186/s40478-015-0218-y · Cited by 93 · see citing works
Discriminative and prognostic potential of cerebrospinal fluid phosphoTau/tau ratio and neurofilaments for frontotemporal dementia subtypes
Pijnenburg, Y. A. L., Verwey, N. A., van der Flier, W. M., Scheltens, P., & Teunissen, C. E. (2015) · Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring · doi:10.1016/j.dadm.2015.11.001 · Cited by 91 · see citing works
Activation of HIPK2 Promotes ER Stress-Mediated Neurodegeneration in Amyotrophic Lateral Sclerosis
Lee, S., Shang, Y., Redmond, S., Urisman, A., Tang, A. A., Li, K. H., Burlingame, A. L., Pak, R. A., Jovičić, A., Gitler, A. D., et al. (2016) · Neuron · doi:10.1016/j.neuron.2016.05.021 · Cited by 85 · see citing works
Unexpected similarities between C9ORF72 and sporadic forms of ALS/FTD suggest a common disease mechanism
Conlon, E. G., Fagegaltier, D., Agius, P., Davis‐Porada, J., Gregory, J. A., Hubbard, I., Kang, K., Kim, D., Phatnani, H. P., Kwan, J. Y., et al. (2018) · eLife · doi:10.7554/elife.37754 · Cited by 85 · see citing works
Executive, language and fluency dysfunction are markers of localised TDP-43 cerebral pathology in non-demented ALS
Gregory, J. M., McDade, K., Bak, T. H., Pal, S., Chandran, S., Smith, C., & Abrahams, S. (2019) · Journal of Neurology Neurosurgery & Psychiatry · doi:10.1136/jnnp-2019-320807 · Cited by 83 · see citing works
Brain morphologic changes in asymptomatic C9orf72 repeat expansion carriers
Walhout, R., Schmidt, R., Westeneng, H., Verstraete, E., Seelen, M., van Rheenen, W., de Reus, M. A., van Es, M. A., Hendrikse, J., Veldink, J. H., et al. (2015) · Neurology · doi:10.1212/wnl.0000000000002135 · Cited by 81 · see citing works
A data-driven approach links microglia to pathology and prognosis in amyotrophic lateral sclerosis
Cooper-Knock, J., Green, C., Altschuler, G., Wei, W., Bury, J. J., Heath, P. R., Wyles, M., Gelsthorpe, C., Highley, J. R., Lorente-Pons, A., et al. (2017) · Acta Neuropathologica Communications · doi:10.1186/s40478-017-0424-x · Cited by 80 · see citing works
ALS Associated Mutations in Matrin 3 Alter Protein-Protein Interactions and Impede mRNA Nuclear Export
Boehringer, A. V., Garcia‐Mansfield, K., Singh, G. M., Bakkar, N., Pirrotte, P., & Bowser, R. P. (2017) · Scientific Reports · doi:10.1038/s41598-017-14924-6 · Cited by 76 · see citing works
Early dipeptide repeat pathology in a frontotemporal dementia kindred with C9ORF72 mutation and intellectual disability
Proudfoot, M. J., Gutowski, N. J., Edbauer, D., Hilton, D. A., Stephens, M., Rankin, J., & Mackenzie, I. R. (2014) · Acta Neuropathologica · doi:10.1007/s00401-014-1245-7 · Cited by 77 · see citing works
Self-citation
Ribonuclease recruitment using a small molecule reduced c9ALS/FTD r(G 4 C 2 ) repeat expansion in vitro and in vivo ALS models
Bush, J. A., Aikawa, H., Fuerst, R., Li, Y., Ursu, A., Meyer, S. M., Benhamou, R. I., Chen, J. L., Khan, T., Wagner-Griffin, S., et al. (2021) · Science Translational Medicine · doi:10.1126/scitranslmed.abd5991 · Cited by 77 · see citing works
Modeling ALS and FTD with iPSC-derived neurons
Lee, S., & Huang, E. J. (2015) · Brain Research · doi:10.1016/j.brainres.2015.10.003 · Cited by 77 · see citing works
TFEB/Mitf links impaired nuclear import to autophagolysosomal dysfunction in C9-ALS
Cunningham, K. M., Maulding, K., Ruan, K., Şentürk, M., Grima, J. C., Sung, H., Zuo, Z., Song, H., Gao, J., Dubey, S. K., et al. (2020) · eLife · doi:10.7554/elife.59419 · Cited by 75 · see citing works
Disruption of ER−mitochondria signalling in fronto-temporal dementia and related amyotrophic lateral sclerosis
Lau, D. H. W., Hartopp, N., Welsh, N. J., Mueller, S., Glennon, E. B. C., Mórotz, G. M., Annibali, A., Gómez‐Suaga, P., Stoica, R., Paillusson, S., et al. (2018) · Cell Death and Disease · doi:10.1038/s41419-017-0022-7 · Cited by 74 · see citing works
Limbic-predominant age-related TDP-43 encephalopathy differs from frontotemporal lobar degeneration
Robinson, J. L., Porta, S., Garrett, F. G., Zhang, P., Xie, S. X., Suh, E. R., Deerlin, V. M. V., Abner, E. L., Jicha, G. A., Barber, J. M., et al. (2020) · Brain · doi:10.1093/brain/awaa219 · Cited by 74 · see citing works
Patterns of cerebral and cerebellar white matter degeneration in ALS: Figure 1
Bede, P., Elamin, M., Byrne, S., McLaughlin, R. L., Kenna, K. P., Vajda, A., Fagan, A. J., Bradley, D. G., & Hardiman, O. M. (2014) · Journal of Neurology Neurosurgery & Psychiatry · doi:10.1136/jnnp-2014-308172 · Cited by 72 · see citing works
C9orf72 promoter hypermethylation is neuroprotective
McMillan, C. T., Russ, J., Wood, E. M., Irwin, D. J., Grossman, M., McCluskey, L. F., Elman, L. B., Deerlin, V. M. V., & Lee, E. B. (2015) · Neurology · doi:10.1212/wnl.0000000000001495 · Cited by 71 · see citing works
Clinical Significance of TDP-43 Neuropathology in Amyotrophic Lateral Sclerosis
Cykowski, M. D., Powell, S. Z.-E., Peterson, L. E., Appel, J. E., Rivera, A. L., Takei, H., Chang, E., & Appel, S. H. (2017) · Journal of Neuropathology & Experimental Neurology · doi:10.1093/jnen/nlx025 · Cited by 67 · see citing works
C9orf72 plays a central role in Rab GTPase-dependent regulation of autophagy
Webster, C. P., Smith, E. F., Grierson, A. J., & Vos, K. J. D. (2016) · Small GTPases · doi:10.1080/21541248.2016.1240495 · Cited by 64 · see citing works
Structural and functional brain signatures of C9orf72 in motor neuron disease
Agosta, F., Ferraro, P. M., Riva, N., Spinelli, E. G., Domi, T., Carrera, P., Copetti, M., Falzone, Y., Ferrari, M., Lunetta, C., et al. (2017) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2017.05.024 · Cited by 63 · see citing works
Current Advances and Limitations in Modeling ALS/FTD in a Dish Using Induced Pluripotent Stem Cells
Guo, W., Fumagalli, L., Prior, R. C., & Bosch, L. V. D. (2017) · Frontiers in Neuroscience · doi:10.3389/fnins.2017.00671 · Cited by 59 · see citing works
Is amyotrophic lateral sclerosis/frontotemporal dementia an autophagy disease?
Deng, Z., Sheehan, P., Chen, S., & Yue, Z. (2017) · Molecular Neurodegeneration · doi:10.1186/s13024-017-0232-6 · Cited by 61 · see citing works
Cryptic exon detection and transcriptomic changes revealed in single-nuclei RNA sequencing of C9ORF72 patients spanning the ALS-FTD spectrum
Gittings, L. M., Alsop, E. B., Antone, J., Singer, M., Whitsett, T. G., Sattler, R., & Keuren‐Jensen, K. R. V. (2023) · Acta Neuropathologica · doi:10.1007/s00401-023-02599-5 · Cited by 56 · see citing works
Neuron loss and degeneration in the progression of TDP-43 in frontotemporal lobar degeneration
Yousef, A., Robinson, J. L., Irwin, D. J., Byrne, M. D., Kwong, L. K., Lee, E. B., Xu, Y., Xie, S. X., Rennert, L., Suh, E. R., et al. (2017) · Acta Neuropathologica Communications · doi:10.1186/s40478-017-0471-3 · Cited by 57 · see citing works
Primary fibroblasts cultures reveal TDP-43 abnormalities in amyotrophic lateral sclerosis patients with and without SOD1 mutations
Sabatelli, M., Zollino, M., Conte, A., Grande, A. D., Marangi, G., Lucchini, M., Massimiliano Mirabella, A., Romano, Â., Piacentini, R., Bisogni, G., et al. (2015) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2015.02.009 · Cited by 56 · see citing works
Loss of exosomes in progranulin-associated frontotemporal dementia
Benussi, L., Ciani, M., Tonoli, E., Morbin, M., Palamara, L., Albani, D., Fusco, F., Forloni, G., Glionna, M., Baco, M., et al. (2016) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2016.01.001 · Cited by 54 · see citing works
C9orf72 and its Relevance in Parkinsonism and Movement Disorders: A Comprehensive Review of the Literature
Bourinaris, T., & Houlden, H. (2018) · Movement Disorders Clinical Practice · doi:10.1002/mdc3.12677 · Cited by 54 · see citing works
Neuropathology of RAN translation proteins in fragile X-associated tremor/ataxia syndrome
Krans, A., Skariah, G., Zhang, Y., Bayly, B., & Todd, P. K. (2019) · Acta Neuropathologica Communications · doi:10.1186/s40478-019-0782-7 · Cited by 51 · see citing works
The Genetics of Monogenic Frontotemporal Dementia
Takada, L. T. (2015) · Dementia & Neuropsychologia · doi:10.1590/1980-57642015dn93000003 · Cited by 51 · see citing works
Old versus New Mechanisms in the Pathogenesis of ALS
Rossi, S., Cozzolino, M., & Carrı̀, M. T. (2016) · Brain Pathology · doi:10.1111/bpa.12355 · Cited by 52 · see citing works
An Assessment of Possible Neuropathology and Clinical Relationships in 46 Sporadic Amyotrophic Lateral Sclerosis Patient Autopsies
Coan, G., & Mitchell, C. S. (2015) · Neurodegenerative Diseases · doi:10.1159/000433581 · Cited by 51 · see citing works
Emotional disorders and the cerebellum: Neurobiological substrates, neuropsychiatry, and therapeutic implications
Schmahmann, J. D. (2021) · Handbook of clinical neurology · doi:10.1016/b978-0-12-822290-4.00016-5 · Cited by 50 · see citing works
Dysregulation of AMPA receptor subunit expression in sporadic ALS post‐mortem brain
Gregory, J. M., Livesey, M. R., McDade, K., Selvaraj, B. T., Barton, S. K., Chandran, S., & Smith, C. (2019) · The Journal of Pathology · doi:10.1002/path.5351 · Cited by 47 · see citing works
Plasma microRNA signature in presymptomatic and symptomatic subjects with C9orf72 -associated frontotemporal dementia and amyotrophic lateral sclerosis
Kmetzsch, V., Anquetil, V., Saracino, D., Rinaldi, D., Camuzat, A., Gareau, T., Jornéa, L., Forlani, S., Couratier, P., Wallon, D., et al. (2020) · Journal of Neurology Neurosurgery & Psychiatry · doi:10.1136/jnnp-2020-324647 · Cited by 47 · see citing works
Current concepts and molecular pathology of neurodegenerative diseases
Forrest, S. L., & Kovács, G. G. (2024) · Pathology · doi:10.1016/j.pathol.2024.10.006 · Cited by 44 · see citing works
Microstructural Changes across Different Clinical Milestones of Disease in Amyotrophic Lateral Sclerosis
Trojsi, F., Caiazzo, G., Corbo, D., Piccirillo, G., Cristillo, V., Femiano, C., Ferrantino, T., Cirillo, M., Monsurrò, M. R., Esposito, F., et al. (2015) · PLoS ONE · doi:10.1371/journal.pone.0119045 · Cited by 43 · see citing works
Pathogenic determinants and mechanisms of ALS/FTD linked to hexanucleotide repeat expansions in the C9orf72 gene
Wen, X., Westergard, T., Pasinelli, P., & Trotti, D. (2016) · Neuroscience Letters · doi:10.1016/j.neulet.2016.09.007 · Cited by 43 · see citing works
Spatial transcriptomics identifies spatially dysregulated expression of GRM3 and USP47 in amyotrophic lateral sclerosis
Gregory, J. M., McDade, K., Livesey, M. R., Croy, I., de Procé, S. M., Aitman, T. J., Chandran, S., & Smith, C. (2020) · Neuropathology and Applied Neurobiology · doi:10.1111/nan.12597 · Cited by 41 · see citing works
Genetic screening of ANXA11 revealed novel mutations linked to amyotrophic lateral sclerosis
Teyssou, E., Muratet, F., Amador, M. D. M., Ferrien, M., Lautrette, G., Machat, S., Boillée, S., Larmonier, T., Saker, S., Leguern, É., et al. (2020) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2020.10.015 · Cited by 42 · see citing works
A toxic gain-of-function mechanism in C9orf72 ALS impairs the autophagy-lysosome pathway in neurons
Beckers, J., Tharkeshwar, A. K., Fumagalli, L., Contardo, M., Schoor, E. V., Fazal, R., Thal, D. R., Chandran, S., Mancuso, R., Bosch, L. V. D., et al. (2023) · Acta Neuropathologica Communications · doi:10.1186/s40478-023-01648-0 · Cited by 40 · see citing works
G2C4 targeting antisense oligonucleotides potently mitigate TDP-43 dysfunction in human C9orf72 ALS/FTD induced pluripotent stem cell derived neurons
Rothstein, J. D., Baskerville, V., Rapuri, S., Mehlhop, E., Jafar‐Nejad, P., Rigo, F., Bennett, F., Mizielinska, S., Isaacs, A. M., & Coyne, A. N. (2023) · Acta Neuropathologica · doi:10.1007/s00401-023-02652-3 · Cited by 40 · see citing works
RNA Misprocessing in C9orf72-Linked Neurodegeneration
Barker, H., Niblock, M., Lee, Y., Shaw, C. E., & Gallo, J. (2017) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2017.00195 · Cited by 39 · see citing works
Synaptic Failure: Focus in an Integrative View of ALS
Casas, C., Manzano, R., Vaz, A. R., Osta, R., & Brites, D. M. T. O. (2015) · Brain Plasticity · doi:10.3233/bpl-140001 · Cited by 36 · see citing works
Recapitulation of Pathological TDP-43 Features in Immortalized Lymphocytes from Sporadic ALS Patients
Posa, D., Martínez‐González, L., Bartolomé, F. B., Nagaraj, S., Porras, G., Martı́nez, A., & Martín‐Requero, Á. (2018) · Molecular Neurobiology · doi:10.1007/s12035-018-1249-8 · Cited by 37 · see citing works
C9orf72-catalyzed GTP loading of Rab39A enables HOPS-mediated membrane tethering and fusion in mammalian autophagy
Zhang, S., Tong, M., Zheng, D., Huang, H., Li, L., Ungermann, C., Pan, Y., Luo, H., Lei, M., Tang, Z., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-42003-0 · Cited by 36 · see citing works
Detection of TDP‐43 seeding activity in the olfactory mucosa from patients with frontotemporal dementia
Fontana, E., Bongianni, M., Benussi, A., Bronzato, E., Scialò, C., Sacchetto, L., Cagnin, A., Castriciano, S., Buratti, E., Gardoni, F., et al. (2023) · Alzheimer s & Dementia · doi:10.1002/alz.13541 · Cited by 34 · see citing works
Update on Hippocampal Sclerosis
Dutra, J. R., Cortes, E. P., & Vonsattel, J. P. (2015) · Current Neurology and Neuroscience Reports · doi:10.1007/s11910-015-0592-7 · Cited by 34 · see citing works
Clinicopathological description of two cases with SQSTM1 gene mutation associated with frontotemporal dementia
Kovács, G. G., van der Zee, J., Hort, J., Kristoferitsch, W., Leitha, T., Höftberger, R., Ströbel, T., Broeckhoven, C. V., & Matěj, R. (2015) · Neuropathology · doi:10.1111/neup.12233 · Cited by 34 · see citing works
Drosha Inclusions Are New Components of Dipeptide-Repeat Protein Aggregates in FTLD-TDP and ALSC9orf72Expansion Cases
Porta, S., Kwong, L. K., Trojanowski, J. Q., & Lee, V. M. ‐. (2015) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/nen.0000000000000182 · Cited by 32 · see citing works
Heritability in frontotemporal dementia: more missing pieces?
Po, K., Leslie, F. V. C., Gracia, N., Bartley, L., Kwok, J. B., Halliday, G. M., Hodges, J. R., & Burrell, J. R. (2014) · Journal of Neurology · doi:10.1007/s00415-014-7474-9 · Cited by 33 · see citing works
Systematic Screening of Ubiquitin/p62 Aggregates in Cerebellar Cortex Expands the Neuropathological Phenotype of the C9orf72 Expansion Mutation
Ramos‐Campoy, O., Polo, R. Á., Grau‐Rivera, O., Antonell, A., Clarimón, J., Rojas‐García, R., Charif, S., Santiago-Valera, V., Hernandez, I., Aguilar, M., et al. (2018) · Journal of Neuropathology & Experimental Neurology · doi:10.1093/jnen/nly047 · Cited by 32 · see citing works
Molecular Pathology of ALS: What We Currently Know and What Important Information Is Still Missing
Jankovská, N., & Matěj, R. (2021) · Diagnostics · doi:10.3390/diagnostics11081365 · Cited by 32 · see citing works
Divergence, Convergence, and Therapeutic Implications: A Cell Biology Perspective of C9ORF72-ALS/FTD
Tang, X., Toro, A., Sahana, T. G., Gao, J., Chalk, J. L., Oskarsson, B., & Zhang, K. (2020) · Molecular Neurodegeneration · doi:10.1186/s13024-020-00383-7 · Cited by 32 · see citing works
Phosphorylated and aggregated TDP-43 with seeding properties are induced upon mutant Huntingtin (mHtt) polyglutamine expression in human cellular models
Coudert, L., Nonaka, T., Bernard, E., Hasegawa, M., Schaeffer, L., & Leblanc, P. (2019) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-019-03059-8 · Cited by 32 · see citing works
Progressive Cerebrocerebellar Uncoupling in Sporadic and Genetic Forms of Amyotrophic Lateral Sclerosis
Tahedl, M., Tan, E. L., Kleinerová, J., Delaney, S., Hengeveld, J. C., Doherty, M. A., McLaughlin, R. L., Pradat, P., Raoul, C., Ango, F., et al. (2024) · Neurology · doi:10.1212/wnl.0000000000209623 · Cited by 30 · see citing works
The emerging role of minor intron splicing in neurological disorders
Jutzi, D., Akinyi, M. V., Mechtersheimer, J., Frilander, M. J., & Ruepp, M. (2018) · Cell Stress · doi:10.15698/cst2018.03.126 · Cited by 29 · see citing works
Altered Phase Separation and Cellular Impact in C9orf72-Linked ALS/FTD
Solomon, D. A., Smikle, R., Reid, M. J., & Mizielinska, S. (2021) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2021.664151 · Cited by 30 · see citing works
Applications of artificial intelligence in dementia research
Tsoi, K. K. F., Jia, P., Dowling, N. M., Titiner, J. R., Wagner, M., Capuano, A. W., & Donohue, M. (2022) · Cambridge Prisms Precision Medicine · doi:10.1017/pcm.2022.10 · Cited by 32 · see citing works
Emerging hiPSC Models for Drug Discovery in Neurodegenerative Diseases
Trudler, D., Ghatak, S., & Lipton, S. A. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22158196 · Cited by 30 · see citing works
Considerations for Clinical Neuropsychological Evaluation in Amyotrophic Lateral Sclerosis
Woolley, S. C., & Rush, B. K. (2017) · Archives of Clinical Neuropsychology · doi:10.1093/arclin/acx089 · Cited by 29 · see citing works
Modelling frontotemporal dementia using patient-derived induced pluripotent stem cells
Lines, G., Casey, J. M., Preza, E., & Wray, S. (2020) · Molecular and Cellular Neuroscience · doi:10.1016/j.mcn.2020.103553 · Cited by 28 · see citing works
ALS skin fibroblasts reveal oxidative stress and ERK1/2-mediated cytoplasmic localization of TDP-43
Romano, N., Catalani, A., Lattante, S., Belardo, A., Proietti, S., Bertini, L., Silvestri, F., Catalani, E., Cervia, D., Zolla, L., et al. (2020) · Cellular Signalling · doi:10.1016/j.cellsig.2020.109591 · Cited by 28 · see citing works

The neuropathology of frontotemporal dementia and amyotrophic lateral sclerosis with a C9ORF72 hexanucleotide repeat expansion
Bieniek, K. F. (n.d.) · ProQuest Demo Repository
Current insights into the C9orf72 repeat expansion diseases of the FTLD/ALS spectrum
Cruts, M., Gijselinck, I., Langenhove, T. V., van der Zee, J., & Broeckhoven, C. V. (2013) · Trends in Neurosciences · doi:10.1016/j.tins.2013.04.010 · Cited by 162 · see citing works
Frontotemporal lobar degeneration with TDP‐43 proteinopathy and chromosome 9p repeat expansion in C9ORF72: clinicopathologic correlation
Bigio, E. H., Weıntraub, S., Rademakers, R., Baker, M. C., Ahmadian, S. S., RADEMAKER, A. W., Weitner, B. B., Mao, Q., Lee, K. ‐., Mishra, M., et al. (2012) · Neuropathology · doi:10.1111/j.1440-1789.2012.01332.x · Cited by 47 · see citing works
Molecular Mechanisms of Neurodegeneration Related to C9orf72 Hexanucleotide Repeat Expansion
Leko, M. B., Župunski, V., Kirincich, J., Smilović, D., Hortobágyi, T., Hof, P. R., & Šimić, G. (2019) · Behavioural Neurology · doi:10.1155/2019/2909168 · Cited by 70 · see citing works
The C9orf72 GGGGCC Repeat Is Translated into Aggregating Dipeptide-Repeat Proteins in FTLD/ALS
Mori, K., Weng, S., Arzberger, T., May, S., Rentzsch, K., Kremmer, E., Schmid, B., Kretzschmar, H. A., Cruts, M., Broeckhoven, C. V., et al. (2013) · Science · doi:10.1126/science.1232927 · Cited by 1,248 · see citing works

Authors: Mackenzie, I. R. A., Frick, P., & Neumann, M.
Affiliations: University of British Columbia (CA)
German Center for Neurodegenerative Diseases (DE)
Corresponding author: Neumann, Manuela
ORCID: Mackenzie, Ian R. A.
Neumann, Manuela
Venue: Acta Neuropathologica
Publisher: Springer Science and Business Media LLC
Published: 2013-12-20
Volume: 127
Issue: 3
Pages: 347-357
ISSN: 0001-6322 (ISSN-L)
1432-0533
DOI: 10.1007/s00401-013-1232-4
OpenAlex: W2121553631
Cited by: 206
References: 69
Citations by year: 2026: 4 · 2025: 6 · 2024: 17 · 2023: 13 · 2022: 20 · 2021: 14 · 2020: 17 · 2019: 17 · 2018: 20 · 2017: 16 · 2016: 23 · 2015: 28 · 2014: 11
FWCI: 2.71
Type: journal article
Language: en
Open access: closed
Licence: www.springer.com/tdm (tdm)
Locations: Acta Neuropathologica (publishedVersion)
PubMed (publishedVersion)
DZNE Pub (submittedVersion)
Funders: Canadian Institutes of Health Research (74580)
Topics: Health Sciences › Medicine › Neurology › Amyotrophic Lateral Sclerosis Research
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Genetic Neurodegenerative Diseases
Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
Keywords: C9orf72, GGGGCC repeat expansion, frontotemporal lobar degeneration, amyotrophic lateral sclerosis, TDP-43, dipeptide repeat proteins, repeat-associated non-AUG translation, ubiquitin-positive inclusions, p62, neurodegeneration, neuropathology, FTLD-TDP
MeSH terms: C9orf72 Protein, Brain, DNA-Binding Proteins, Humans, Phenotype, Proteins, Neurodegenerative Diseases, DNA Repeat Expansion, Frontotemporal Lobar Degeneration

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The neuropathology associated with repeat expansions in the C9ORF72 gene

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