Null mutations in progranulin cause ubiquitin-positive frontotemporal dementia linked to chromosome 17q21
Abstract
Frontotemporal dementia (FTD) with ubiquitin-immunoreactive neuronal inclusions (both cytoplasmic and nuclear) of unknown nature has been linked to a chromosome 17q21 region (FTDU-17) containing MAPT (microtubule-associated protein tau). FTDU-17 patients have consistently been shown to lack a tau-immunoreactive pathology, a feature characteristic of FTD with parkinsonism linked to mutations in MAPT (FTDP-17). Furthermore, in FTDU-17 patients, mutations in MAPT and genomic rearrangements in the MAPT region have been excluded by both genomic sequencing and fluorescence in situ hybridization on mechanically stretched chromosomes. Here we demonstrate that FTDU-17 is caused by mutations in the gene coding for progranulin (PGRN), a growth factor involved in multiple physiological and pathological processes including tumorigenesis. Besides the production of truncated PGRN proteins due to premature stop codons, we identified a mutation within the splice donor site of intron 0 (IVS0 + 5G > C), indicating loss of the mutant transcript by nuclear degradation. The finding was made within an extensively documented Belgian FTDU-17 founder family. Transcript and protein analyses confirmed the absence of the mutant allele and a reduction in the expression of PGRN. We also identified a mutation (c.3G > A) in the Met1 translation initiation codon, indicating loss of PGRN due to lack of translation of the mutant allele. Our data provide evidence that PGRN haploinsufficiency leads to neurodegeneration because of reduced PGRN-mediated neuronal survival. Furthermore, in a Belgian series of familial FTD patients, PGRN mutations were 3.5 times more frequent than mutations in MAPT, underscoring a principal involvement of PGRN in FTD pathogenesis.
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Upon signaling from neurons, PLP is exocytosed to the plasma membrane to form the myelin sheath.
“Upon signaling from neurons, PLP is exocytosed to the plasma membrane to form the myelin sheath.37”
From The lysosome and proteostatic stress at the intersection of pediatric neurological disorders and adult neurodegenerative diseases (2025) · cites this paper as [37]
A proteomic relationship between Alzheimer's disease and FTD is supported by TREM2 mutations causing microglial dysfunction and leading to Alzheimer's disease, and PGRN mutations causing microglial dysfunction and leading to FTD.
“A proteomic relationship between AD and FTD is supported by the fact that mutations in the triggering receptor expressed on myeloid cells 2 (TREM2) protein cause microglial dysfunction and lead to AD39,40, whereas mutations in the progranulin (PGRN) protein also cause microglial dysfunction and lead to FTD41–43.”
Power calculations estimated that ~99K cases, ~2.3 times more than this work, would be needed for a variant with minor allele frequency 21.3% and effect estimate 0.047 to reach genome-wide significance at 80% power.
“We performed power calculations to forecast the number of additional PD cases needed to achieve genome-wide significance at 80% power for a variant with a minor allele frequency of 21.3% and an effect estimate of 0.047 (32). Assuming that future data is well-harmonized with current data and that disease prevalence is 0.5%, we estimated that we would need a total of ~99K cases, ~2.3 times more than”
From Identification of novel risk loci, causal insights, and heritable risk for Parkinson's disease: a meta-analysis of genome-wide association studies (2019) · cites this paper as [32]
Cites
Association of missense and 5′-splice-site mutations in tau with the inherited dementia FTDP-17
Hutton, M., Lendon, C. L., Rizzu, P., Baker, M., Froelich, S., Houlden, H., Pickering-Brown, S., Chakraverty, S., Isaacs, A., Grover, A., et al. (1998) · Nature · doi:10.1038/31508 · Cited by 3,498 · see citing works
Mutations in progranulin cause tau-negative frontotemporal dementia linked to chromosome 17
Baker, M., Mackenzie, I. R., Pickering-Brown, S. M., Gass, J., Rademakers, R., Lindholm, C., Snowden, J., Adamson, J., Sadovnick, A. D., Rollinson, S., et al. (2006) · Nature · doi:10.1038/nature05016 · Cited by 2,058 · see citing works
Self-citationMutant valosin‐containing protein causes a novel type of frontotemporal dementia
Schröder, R., Watts, G. D. J., Mehta, S. G., Evert, B. O., Broich, P., Fließbach, K., Pauls, K., Hans, V. H., Kimonis, V., & Thal, D. R. (2005) · Annals of Neurology · doi:10.1002/ana.20407 · Cited by 177 · see citing works
Progranulin mutations in ubiquitin-positive frontotemporal dementia linked to chromosome 17q21
Cruts, M., Kumar-Singh, S., & Van Broeckhoven, C. (2006) · Current Alzheimer Research · doi:10.2174/156720506779025251 · Cited by 67 · see citing works
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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
Sensitivity of revised diagnostic criteria for the behavioural variant of frontotemporal dementia
Rascovsky, K., Hodges, J. R., Knopman, D., Mendez, M. F., Kramer, J. H., Neuhaus, J., van Swieten, J. C., Seelaar, H., Dopper, E. G. P., Onyike, C. U., et al. (2011) · Brain · doi:10.1093/brain/awr179 · Cited by 5,221 · see citing works
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-citationArai, T., Hasegawa, M., Akiyama, H., Ikeda, K., Nonaka, T., Mori, H., Mann, D., Tsuchiya, K., Yoshida, M., Hashizume, Y., et al. (2006) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2006.10.093 · Cited by 2,732 · see citing works
Nalls, M. A., Blauwendraat, C., Vallerga, C. L., Heilbron, K., Bandres-Ciga, S., Chang, D., Tan, M., Kia, D. A., Noyce, A. J., Xue, A., et al. (2019) · The Lancet Neurology · doi:10.1016/s1474-4422(19)30320-5 · Cited by 2,454 · see citing works
Mutations in progranulin cause tau-negative frontotemporal dementia linked to chromosome 17
Baker, M., Mackenzie, I. R., Pickering-Brown, S. M., Gass, J., Rademakers, R., Lindholm, C., Snowden, J., Adamson, J., Sadovnick, A. D., Rollinson, S., et al. (2006) · Nature · doi:10.1038/nature05016 · Cited by 2,058 · see citing works
Self-citationConverging Mechanisms in ALS and FTD: Disrupted RNA and Protein Homeostasis
Ling, S.-C., Polymenidou, M., & Cleveland, D. W. (2013) · Neuron · doi:10.1016/j.neuron.2013.07.033 · Cited by 1,811 · see citing works
Limbic-predominant age-related TDP-43 encephalopathy (LATE): consensus working group report
Nelson, P. T., Dickson, D. W., Trojanowski, J. Q., Jack, C. R., Boyle, P. A., Arfanakis, K., Rademakers, R., Alafuzoff, I., Attems, J., Brayne, C., et al. (2019) · Brain · doi:10.1093/brain/awz099 · Cited by 1,547 · see citing works
Self-citationLong pre-mRNA depletion and RNA missplicing contribute to neuronal vulnerability from loss of TDP-43
Polymenidou, M., Lagier-Tourenne, C., Hutt, K. R., Huelga, S. C., Moran, J., Liang, T. Y., Ling, S.-C., Sun, E., Wancewicz, E., Mazur, C., et al. (2011) · Nature Neuroscience · doi:10.1038/nn.2779 · Cited by 1,335 · see citing works
Tau pathology and neurodegeneration
Spillantini, M. G., & Goedert, M. (2013) · The Lancet Neurology · doi:10.1016/s1474-4422(13)70090-5 · Cited by 1,133 · see citing works
Cairns, N. J., Bigio, E. H., Mackenzie, I. R. A., Neumann, M., Lee, V. M.-Y., Hatanpaa, K. J., White, C. L., Schneider, J. A., Grinberg, L. T., Halliday, G., et al. (2007) · Acta Neuropathologica · doi:10.1007/s00401-007-0237-2 · Cited by 1,110 · see citing works
TDP-43 and FUS/TLS: emerging roles in RNA processing and neurodegeneration
Lagier-Tourenne, C., Polymenidou, M., & Cleveland, D. W. (2010) · Human Molecular Genetics · doi:10.1093/hmg/ddq137 · Cited by 1,021 · see citing works
Johnson, E. C. B., Dammer, E. B., Duong, D. M., Ping, L., Zhou, M., Yin, L., Higginbotham, L. A., Guajardo, A., White, B., Troncoso, J. C., et al. (2020) · Nature Medicine · doi:10.1038/s41591-020-0815-6 · Cited by 1,001 · see citing works
Parkinson’s disease: genetics and pathogenesis
Shulman, J. M., De Jager, P. L., & Feany, M. B. (2011) · Annual Review of Pathology: Mechanisms of Disease · doi:10.1146/annurev-pathol-011110-130242 · Cited by 801 · see citing works
Tang, W., Lu, Y., Tian, Q.-Y., Zhang, Y., Guo, F.-J., Liu, G.-Y., Syed, N. M., Lai, Y., Lin, E. A., Kong, L., et al. (2011) · Science · doi:10.1126/science.1199214 · Cited by 761 · see citing works
Semantic dementia: a unique clinicopathological syndrome
Hodges, J. R., & Patterson, K. (2007) · The Lancet Neurology · doi:10.1016/s1474-4422(07)70266-1 · Cited by 772 · see citing works
Lui, H., Zhang, J., Makinson, S. R., Cahill, M. K., Kelley, K. W., Huang, H.-Y., Shang, Y., Oldham, M. C., Martens, L. H., Gao, F., et al. (2016) · Cell · doi:10.1016/j.cell.2016.04.001 · Cited by 729 · see citing works
Self-citationYankner, B. A., Lu, T., & Loerch, P. (2008) · Annual Review of Pathology: Mechanisms of Disease · doi:10.1146/annurev.pathmechdis.2.010506.092044 · Cited by 677 · 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
Clinical, genetic and pathological heterogeneity of frontotemporal dementia: A review
Seelaar, H., Rohrer, J. D., Pijnenburg, Y. A. L., Fox, N. C., & van Swieten, J. C. (2011) · Journal of Neurology, Neurosurgery & Psychiatry · doi:10.1136/jnnp.2010.212225 · Cited by 609 · see citing works
<i>C9orf72</i> is required for proper macrophage and microglial function in mice
O’Rourke, J. G., Bogdanik, L., Yáñez, A., Lall, D., Wolf, A. J., Muhammad, A. K. M. G., Ho, R., Carmona, S., Vit, J. P., Zarrow, J., et al. (2016) · Science · doi:10.1126/science.aaf1064 · Cited by 550 · see citing works
The heritability and genetics of frontotemporal lobar degeneration
Rohrer, J. D., Guerreiro, R., Vandrovcova, J., Uphill, J., Reiman, D., Beck, J., Isaacs, A. M., Authier, A., Ferrari, R., Fox, N. C., et al. (2009) · Neurology · doi:10.1212/wnl.0b013e3181bf997a · Cited by 536 · see citing works
The epidemiology of frontotemporal dementia
Onyike, C. U., & Diehl-Schmid, J. (2013) · International Review of Psychiatry · doi:10.3109/09540261.2013.776523 · Cited by 543 · see citing works
Gowrishankar, S., Yuan, P., Wu, Y., Schrag, M., Paradise, S., Grutzendler, J., De Camilli, P., & Ferguson, S. M. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1510329112 · Cited by 406 · see citing works
Neuroimaging signatures of frontotemporal dementia genetics: C9ORF72, tau, progranulin and sporadics
Whitwell, J. L., Weigand, S. D., Boeve, B. F., Senjem, M. L., Gunter, J. L., DeJesus-Hernandez, M., Rutherford, N. J., Baker, M., Knopman, D. S., Wszolek, Z. K., et al. (2012) · Brain · doi:10.1093/brain/aws001 · Cited by 397 · see citing works
Self-citationALS Genetics: Gains, Losses, and Implications for Future Therapies
Kim, G., Gautier, O., Tassoni-Tsuchida, E., Ma, X. R., & Gitler, A. D. (2020) · Neuron · doi:10.1016/j.neuron.2020.08.022 · Cited by 370 · see citing works
Guerreiro, R. J., Lohmann, E., Brás, J. M., Gibbs, J. R., Rohrer, J. D., Gurunlian, N., Dursun, B., Bilgic, B., Hanagasi, H., Gurvit, H., et al. (2013) · JAMA Neurology · doi:10.1001/jamaneurol.2013.579 · Cited by 374 · see citing works
Frontotemporal dementia and its subtypes: a genome-wide association study
Ferrari, R., Hernandez, D. G., Nalls, M. A., Rohrer, J. D., Ramasamy, A., Kwok, J. B. J., Dobson-Stone, C., Brooks, W. S., Schofield, P. R., Halliday, G. M., et al. (2014) · The Lancet Neurology · doi:10.1016/s1474-4422(14)70065-1 · Cited by 383 · see citing works
Self-citationEarly frontotemporal dementia targets neurons unique to apes and humans
Seeley, W. W., Carlin, D. A., Allman, J. M., Macedo, M. N., Bush, C., Miller, B. L., & DeArmond, S. J. (2006) · Annals of Neurology · doi:10.1002/ana.21055 · Cited by 364 · see citing works
Loy, C. T., Schofield, P. R., Turner, A. M., & Kwok, J. B. (2014) · The Lancet · doi:10.1016/s0140-6736(13)60630-3 · Cited by 342 · see citing works
Neurovascular signalling defects in neurodegeneration
Zacchigna, S., Lambrechts, D., & Carmeliet, P. (2008) · Nature Reviews Neuroscience · doi:10.1038/nrn2336 · Cited by 345 · see citing works
Moore, K. M., Nicholas, J., Grossman, M., McMillan, C. T., Irwin, D. J., Massimo, L., Van Deerlin, V. M., Warren, J. D., Fox, N. C., Rossor, M. N., et al. (2020) · The Lancet Neurology · doi:10.1016/s1474-4422(19)30394-1 · Cited by 313 · see citing works
Self-citationProgressive Supranuclear Palsy: Pathology and Genetics
Dickson, D. W., Rademakers, R., & Hutton, M. L. (2007) · Brain Pathology · doi:10.1111/j.1750-3639.2007.00054.x · Cited by 314 · see citing works
Self-citationPottier, C., Bieniek, K. F., Finch, N., van de Vorst, M., Baker, M., Perkersen, R., Brown, P., Ravenscroft, T., van Blitterswijk, M., Nicholson, A. M., et al. (2015) · Acta Neuropathologica · doi:10.1007/s00401-015-1436-x · Cited by 312 · see citing works
Self-citationThe identity and function of microglia in neurodegeneration
Song, W. M., & Colonna, M. (2018) · Nature Immunology · doi:10.1038/s41590-018-0212-1 · Cited by 308 · see citing works
Neuroinflammation in frontotemporal dementia
Bright, F., Werry, E. L., Dobson-Stone, C., Piguet, O., Ittner, L. M., Halliday, G. M., Hodges, J. R., Kiernan, M. C., Loy, C. T., Kassiou, M., et al. (2019) · Nature Reviews Neurology · doi:10.1038/s41582-019-0231-z · Cited by 280 · see citing works
The genetics and neuropathology of frontotemporal lobar degeneration
Sieben, A., Van Langenhove, T., Engelborghs, S., Martin, J.-J., Boon, P., Cras, P., De Deyn, P.-P., Santens, P., Van Broeckhoven, C., & Cruts, M. (2012) · Acta Neuropathologica · doi:10.1007/s00401-012-1029-x · Cited by 280 · see citing works
Self-citationAnalysis of alternative splicing associated with aging and neurodegeneration in the human brain
Tollervey, J. R., Wang, Z., Hortobágyi, T., Witten, J. T., Zarnack, K., Kayikci, M., Clark, T. A., Schweitzer, A. C., Rot, G., Curk, T., et al. (2011) · Genome Research · doi:10.1101/gr.122226.111 · Cited by 252 · see citing works
Finch, N., Carrasquillo, M. M., Baker, M., Rutherford, N. J., Coppola, G., DeJesus-Hernandez, M., Crook, R., Hunter, T., Ghidoni, R., Benussi, L., et al. (2011) · Neurology · doi:10.1212/wnl.0b013e31820a0e3b · Cited by 243 · see citing works
Self-citationProgranulin protects against amyloid β deposition and toxicity in Alzheimer's disease mouse models
Minami, S. S., Min, S.-W., Krabbe, G., Wang, C., Zhou, Y., Asgarov, R., Li, Y., Martens, L. H., Elia, L. P., Ward, M. E., et al. (2014) · Nature Medicine · doi:10.1038/nm.3672 · Cited by 237 · see citing works
The lysosomal function of progranulin, a guardian against neurodegeneration
Paushter, D. H., Du, H., Feng, T., & Hu, F. (2018) · Acta Neuropathologica · doi:10.1007/s00401-018-1861-8 · Cited by 230 · see citing works
Logan, T., Simon, M. J., Rana, A., Cherf, G. M., Srivastava, A., Davis, S. S., Low, R. L. Y., Chiu, C.-L., Fang, M., Huang, F., et al. (2021) · Cell · doi:10.1016/j.cell.2021.08.002 · Cited by 233 · see citing works
Moisse, K., Volkening, K., Leystra-Lantz, C., Welch, I., Hill, T., & Strong, M. J. (2009) · Brain Research · doi:10.1016/j.brainres.2008.10.021 · Cited by 210 · see citing works
Geser, F., Lee, V. M.-Y., & Trojanowski, J. Q. (2010) · Neuropathology · doi:10.1111/j.1440-1789.2009.01091.x · Cited by 195 · see citing works
Yu, C.-E., Bird, T. D., Bekris, L. M., Montine, T. J., Leverenz, J. B., Steinbart, E., Galloway, N. M., Feldman, H., Woltjer, R., Miller, C. A., et al. (2010) · Archives of Neurology · doi:10.1001/archneurol.2009.328 · Cited by 190 · see citing works
Targeting microglia for the treatment of Alzheimer’s Disease
Wes, P. D., Sayed, F. A., Bard, F., & Gan, L. (2016) · Glia · doi:10.1002/glia.22988 · Cited by 185 · see citing works
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
Long, J. M., Ray, B., & Lahiri, D. K. (2014) · Journal of Biological Chemistry · doi:10.1074/jbc.m113.518241 · Cited by 187 · see citing works
Frontotemporal lobar degeneration
Grossman, M., Seeley, W. W., Boxer, A. L., Hillis, A. E., Knopman, D. S., Ljubenov, P. A., Miller, B., Piguet, O., Rademakers, R., Whitwell, J. L., et al. (2023) · Nature Reviews Disease Primers · doi:10.1038/s41572-023-00447-0 · Cited by 178 · see citing works
Self-citationBer, I. L., Guedj, E., Gabelle, A., Verpillat, P., Volteau, M., Thomas-Anterion, C., Decousus, M., Hannequin, D., Vera, P., Lacomblez, L., et al. (2006) · Brain · doi:10.1093/brain/awl288 · Cited by 179 · see citing works
Yin, F., Dumont, M., Banerjee, R., Ma, Y., Li, H., Lin, M. T., Beal, M. F., Nathan, C., Thomas, B., & Ding, A. (2010) · The FASEB Journal · doi:10.1096/fj.10-161471 · Cited by 180 · see citing works
Microglia and C9orf72 in neuroinflammation and ALS and frontotemporal dementia
Lall, D., & Baloh, R. H. (2017) · Journal of Clinical Investigation · doi:10.1172/jci90607 · Cited by 175 · see citing works
Caccamo, A., Majumder, S., Deng, J. J., Bai, Y., Thornton, F. B., & Oddo, S. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.031278 · Cited by 169 · see citing works
van der Zee, J., Urwin, H., Engelborghs, S., Bruyland, M., Vandenberghe, R., Dermaut, B., De Pooter, T., Peeters, K., Santens, P., De Deyn, P. P., et al. (2008) · Human Molecular Genetics · doi:10.1093/hmg/ddm309 · Cited by 167 · see citing works
Self-citationFrontotemporal dementia and related disorders: Deciphering the enigma
Josephs, K. A. (2008) · Annals of Neurology · doi:10.1002/ana.21426 · Cited by 166 · see citing works
<i>Progranulin</i> genetic variability contributes to amyotrophic lateral sclerosis
Sleegers, K., Brouwers, N., Maurer-Stroh, S., van Es, M. A., Damme, P. V., van Vught, P. W. J., van der Zee, J., Serneels, S., Pooter, T. D., Van den Broeck, M., et al. (2008) · Neurology · doi:10.1212/01.wnl.0000289191.54852.75 · Cited by 161 · see citing works
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Nelson, P. T., Trojanowski, J. Q., Abner, E. L., Al-Janabi, O. M., Jicha, G. A., Schmitt, F. A., Smith, C. D., Fardo, D. W., Wang, W.-X., Kryscio, R. J., et al. (2016) · Journal of Neuropathology & Experimental Neurology · doi:10.1093/jnen/nlw033 · Cited by 158 · see citing works
Review: neuropathology of non-tau frontotemporal lobar degeneration
Neumann, M., & Mackenzie, I. R. A. (2019) · Neuropathology and Applied Neurobiology · doi:10.1111/nan.12526 · Cited by 144 · see citing works
C9orf72 deficiency promotes microglial-mediated synaptic loss in aging and amyloid accumulation
Lall, D., Lorenzini, I., Mota, T. A., Bell, S., Mahan, T. E., Ulrich, J. D., Davtyan, H., Rexach, J. E., Muhammad, A. K. M. G., Shelest, O., et al. (2021) · Neuron · doi:10.1016/j.neuron.2021.05.020 · Cited by 147 · see citing works
Progranulin deficiency causes impairment of autophagy and TDP-43 accumulation
Chang, M. C., Srinivasan, K., Friedman, B. A., Suto, E., Modrusan, Z., Lee, W. P., Kaminker, J. S., Hansen, D. V., & Sheng, M. (2017) · Journal of Experimental Medicine · doi:10.1084/jem.20160999 · Cited by 141 · see citing works
Progranulin: a new avenue towards the understanding and treatment of neurodegenerative disease
Chitramuthu, B. P., Bennett, H. P. J., & Bateman, A. (2017) · Brain · doi:10.1093/brain/awx198 · Cited by 138 · see citing works
Pottier, C., Zhou, X., Perkerson, R. B., Baker, M., Jenkins, G. D., Serie, D. J., Ghidoni, R., Benussi, L., Binetti, G., López de Munain, A., et al. (2018) · The Lancet Neurology · doi:10.1016/s1474-4422(18)30126-1 · Cited by 131 · see citing works
Self-citationChen-Plotkin, A. S., Geser, F., Plotkin, J. B., Clark, C. M., Kwong, L. K., Yuan, W., Grossman, M., Van Deerlin, V. M., Trojanowski, J. Q., & Lee, V. M.-Y. (2008) · Human Molecular Genetics · doi:10.1093/hmg/ddn023 · Cited by 135 · see citing works
Frontotemporal Lobar Degeneration: Epidemiology, Pathology, Diagnosis and Management
Seltman, R. E., & Matthews, B. R. (2012) · CNS Drugs · doi:10.2165/11640070-000000000-00000 · Cited by 132 · see citing works
Cytoplasmic accumulation and aggregation of TDP-43 upon proteasome inhibition in cultured neurons.
van Eersel, J., Ke, Y. D., Gladbach, A., Bi, M., Götz, J., Kril, J. J., & Ittner, L. M. (2011) · PLoS ONE · doi:10.1371/journal.pone.0022850 · Cited by 130 · see citing works
Leverenz, J. B., Yu, C. E., Montine, T. J., Steinbart, E., Bekris, L. M., Zabetian, C., Kwong, L. K., Lee, V. M.-Y., Schellenberg, G. D., & Bird, T. D. (2007) · Brain · doi:10.1093/brain/awm069 · Cited by 129 · see citing works
Rosen, E. Y., Wexler, E. M., Versano, R., Coppola, G., Gao, F., Winden, K. D., Oldham, M. C., Martens, L. H., Zhou, P., Farese, R. V., et al. (2011) · Neuron · doi:10.1016/j.neuron.2011.07.021 · Cited by 128 · see citing works
Feng, T., Lacrampe, A., & Hu, F. (2021) · Acta Neuropathologica · doi:10.1007/s00401-020-02246-3 · Cited by 110 · see citing works
Progressive neuronal inclusion formation and axonal degeneration in CHMP2B mutant transgenic mice
Ghazi-Noori, S., Froud, K. E., Mizielinska, S., Powell, C., Smidak, M., Fernandez de Marco, M., O’Malley, C., Farmer, M., Parkinson, N., Fisher, E. M. C., et al. (2012) · Brain · doi:10.1093/brain/aws006 · Cited by 115 · see citing works
Suárez‐Calvet, M., Capell, A., Araque Caballero, M. Á., Morenas‐Rodríguez, E., Fellerer, K., Franzmeier, N., Kleinberger, G., Eren, E., Deming, Y., Piccio, L., et al. (2018) · EMBO Molecular Medicine · doi:10.15252/emmm.201809712 · Cited by 109 · see citing works
Progranulin is a chemoattractant for microglia and stimulates their endocytic activity
Pickford, F., Marcus, J., Camargo, L. M., Xiao, Q., Graham, D., Mo, J.-R., Burkhardt, M., Kulkarni, V., Crispino, J., Hering, H., et al. (2011) · The American Journal of Pathology · doi:10.1016/j.ajpath.2010.11.002 · Cited by 107 · see citing works
Van Mossevelde, S., van der Zee, J., Gijselinck, I., Engelborghs, S., Sieben, A., Van Langenhove, T., De Bleecker, J., Baets, J., Vandenbulcke, M., Van Laere, K., et al. (2016) · Brain · doi:10.1093/brain/awv358 · Cited by 98 · see citing works
Self-citationReifschneider, A., Robinson, S., van Lengerich, B., Gnörich, J., Logan, T., Heindl, S., Vogt, M. A., Weidinger, E., Riedl, L., Wind, K., et al. (2022) · The EMBO Journal · doi:10.15252/embj.2021109108 · Cited by 89 · see citing works
Homozygous GRN mutations: new phenotypes and new insights into pathological and molecular mechanisms
Huin, V., Barbier, M., Bottani, A., Lobrinus, J. A., Clot, F., Lamari, F., Chat, L., Rucheton, B., Fluchère, F., Auvin, S., et al. (2020) · Brain · doi:10.1093/brain/awz377 · Cited by 96 · see citing works
Irwin, D. J., Trojanowski, J. Q., & Grossman, M. (2013) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2013.00006 · Cited by 96 · see citing works
Nuclear pore complexes — a doorway to neural injury in neurodegeneration
Coyne, A. N., & Rothstein, J. D. (2022) · Nature Reviews Neurology · doi:10.1038/s41582-022-00653-6 · Cited by 96 · see citing works
Moisse, K., Mepham, J., Volkening, K., Welch, I., Hill, T., & Strong, M. J. (2009) · Brain Research · doi:10.1016/j.brainres.2009.07.023 · Cited by 93 · see citing works
Womack, K. B., Diaz-Arrastia, R., Aizenstein, H. J., Arnold, S. E., Barbas, N. R., Boeve, B. F., Clark, C. M., DeCarli, C. S., Jagust, W. J., Leverenz, J. B., et al. (2011) · Archives of Neurology · doi:10.1001/archneurol.2010.295 · Cited by 85 · see citing works
Characteristics of frontotemporal dementia patients with a <i>Progranulin</i> mutation
Huey, E. D., Grafman, J., Wassermann, E. M., Pietrini, P., Tierney, M. C., Ghetti, B., Spina, S., Baker, M., Hutton, M., Elder, J. W., et al. (2006) · Annals of Neurology · doi:10.1002/ana.20969 · Cited by 87 · see citing works
Ramos, E. M., Dokuru, D. R., Van Berlo, V., Wojta, K., Wang, Q., Huang, A. Y., Deverasetty, S., Qin, Y., van Blitterswijk, M., Jackson, J., et al. (2020) · Alzheimer's & Dementia · doi:10.1002/alz.12011 · Cited by 80 · see citing works
Self-citationProgranulin Gene Delivery Protects Dopaminergic Neurons in a Mouse Model of Parkinson’s Disease
Van Kampen, J. M., Baranowski, D., & Kay, D. G. (2014) · PLoS ONE · doi:10.1371/journal.pone.0097032 · Cited by 76 · see citing works
Csf p-tau<sub>181</sub>/tau ratio as biomarker for TDP pathology in frontotemporal dementia
Borroni, B., Benussi, A., Archetti, S., Galimberti, D., Parnetti, L., Nacmias, B., Sorbi, S., Scarpini, E., & Padovani, A. (2015) · Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration · doi:10.3109/21678421.2014.971812 · Cited by 77 · see citing works
Boeve, B. F. (2007) · Alzheimer Disease & Associated Disorders · doi:10.1097/wad.0b013e31815bf454 · Cited by 73 · see citing works
Wexler, E. M., Rosen, E., Lu, D., Osborn, G. E., Martin, E., Raybould, H., & Geschwind, D. H. (2011) · Science Signaling · doi:10.1126/scisignal.2002282 · Cited by 56 · see citing works
Remnestål, J., Öijerstedt, L., Ullgren, A., Olofsson, J., Bergström, S., Kultima, K., Ingelsson, M., Kilander, L., Uhlén, M., Månberg, A., et al. (2020) · Translational Neurodegeneration · doi:10.1186/s40035-020-00198-y · Cited by 56 · see citing works
FTD spectrum: Neuroimaging across the FTD spectrum
Whitwell, J. L. (2019) · Progress in Molecular Biology and Translational Science · doi:10.1016/bs.pmbts.2019.05.009 · Cited by 53 · see citing works
Advances in treatment of frontotemporal dementia
Magrath Guimet, N., Zapata-Restrepo, L. M., & Miller, B. L. (2022) · The Journal of Neuropsychiatry and Clinical Neurosciences · doi:10.1176/appi.neuropsych.21060166 · Cited by 52 · see citing works
Association of progranulin polymorphism rs5848 with neurodegenerative diseases: a meta-analysis
Chen, Y., Li, S., Su, L., Sheng, J., Lv, W., Chen, G., & Xu, Z. (2015) · Journal of Neurology · doi:10.1007/s00415-014-7630-2 · Cited by 50 · see citing works
Genetics of Gene Expression in the Aging Human Brain Reveal TDP-43 Proteinopathy Pathophysiology
Yang, H.-S., White, C. C., Klein, H.-U., Yu, L., Gaiteri, C., Ma, Y., Felsky, D., Mostafavi, S., Petyuk, V. A., Sperling, R. A., et al. (2020) · Neuron · doi:10.1016/j.neuron.2020.05.010 · Cited by 47 · see citing works
Heuer, H. W., Wang, P., Rascovsky, K., Wolf, A., Appleby, B., Bove, J., Bordelon, Y., Brannelly, P., Brushaber, D. E., Caso, C., et al. (2020) · Alzheimer's & Dementia · doi:10.1002/alz.12046 · Cited by 43 · see citing works
Self-citationGenetic risk factors for Alzheimer disease: emerging roles of microglia in disease pathomechanisms
Takatori, S., Wang, W., Iguchi, A., & Tomita, T. (2019) · Advances in Experimental Medicine and Biology · doi:10.1007/978-3-030-05542-4_5 · Cited by 44 · see citing works
WDR41 supports lysosomal response to changes in amino acid availability
Amick, J., Tharkeshwar, A. K., Amaya, & Ferguson, S. M. (2018) · Molecular Biology of the Cell · doi:10.1091/mbc.e17-12-0703 · Cited by 39 · see citing works
Root, J., Mendsaikhan, A., Taylor, G., Merino, P., Nandy, S., Wang, M., Araujo, L. T., Ryu, D., Holler, C., Thompson, B. M., et al. (2024) · Cell Reports · doi:10.1016/j.celrep.2024.114985 · Cited by 39 · see citing works
Sha, S. J., Miller, Z. A., Min, S., Zhou, Y., Brown, J., Mitic, L. L., Karydas, A., Koestler, M., Tsai, R., Corbetta‐Rastelli, C., et al. (2017) · Alzheimer's & Dementia: Translational Research & Clinical Interventions · doi:10.1016/j.trci.2017.08.002 · Cited by 36 · see citing works
AZP2006, a new promising treatment for Alzheimer’s and related diseases
Callizot, N., Estrella, C., Burlet, S., Henriques, A., Brantis, C., Barrier, M., Campanari, M. L., & Verwaerde, P. (2021) · Scientific Reports · doi:10.1038/s41598-021-94708-1 · Cited by 35 · see citing works
Gossye, H., Van Broeckhoven, C., & Engelborghs, S. (2019) · Frontiers in Neuroscience · doi:10.3389/fnins.2019.00757 · Cited by 34 · see citing works
Self-citationFrontotemporal dementia: Past, present, and future
Ulugut, H., & Pijnenburg, Y. A. L. (2023) · Alzheimer's & Dementia · doi:10.1002/alz.13363 · Cited by 33 · see citing works
Telpoukhovskaia, M. A., Liu, K., Sayed, F. A., Etchegaray, J. I., Xie, M., Zhan, L., Li, Y., Zhou, Y., Le, D., Bahr, B. A., et al. (2020) · Scientific Reports · doi:10.1038/s41598-020-70534-9 · Cited by 23 · see citing works
Josephs, K. A. (2018) · Brain · doi:10.1093/brain/awx367 · Cited by 17 · see citing works
The role of macrophage scavenger receptor 1 (Msr1) in prion pathogenesis
Li, B., Chen, M., Aguzzi, A., & Zhu, C. (2021) · Journal of Molecular Medicine · doi:10.1007/s00109-021-02061-7 · Cited by 7 · see citing works
- Authors
- Cruts, M., Gijselinck, I., van der Zee, J., Engelborghs, S., Wils, H., Pirici, D., Rademakers, R., Vandenberghe, R., Dermaut, B., Martin, J.-J., van Duijn, C., Peeters, K., Sciot, R., Santens, P., De Pooter, T., Mattheijssens, M., Van den Broeck, M., Cuijt, I., Vennekens, K., De Deyn, P. P., Kumar-Singh, S., & Van Broeckhoven, C.
- Affiliations
- Vlaams Instituut voor Biotechnologie (BE)
- University of Antwerp (BE)
- Ghent University Hospital (BE)
- KU Leuven (BE)
- ORCID
- Venue
- Nature
- Published
- 2006-07-16
- Volume
- 442
- Issue
- 7105
- Pages
- 920-924
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W2005731595
- Cited by
- 1,512
- References
- 4
- Citations by year
- 2026: 32 · 2025: 50 · 2024: 53 · 2023: 56 · 2022: 52 · 2021: 73 · 2020: 67 · 2019: 83 · 2018: 68 · 2017: 82 · 2016: 78 · 2015: 55 · 2014: 78 · 2013: 77 · 2012: 90
- FWCI
- 77.47
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (submittedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Ghent University Academic Bibliography (Ghent University) (submittedVersion)
- VUBIR (Vrije Universiteit Brussel) (submittedVersion)
- Topics
- Health Sciences › Medicine › Neurology › Amyotrophic Lateral Sclerosis Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- progranulin, frontotemporal dementia, chromosome 17q21, haploinsufficiency, splice donor site mutation, premature stop codon, MAPT, tau protein, neurodegeneration
- MeSH terms
- Progranulins, Belgium, Chromosomes, Human, Pair 17, Dementia, DNA Mutational Analysis, Frontal Lobe, Humans, Genetic Linkage, Mutation, Temporal Lobe, Physical Chromosome Mapping, RNA Splice Sites, Ubiquitin, Intercellular Signaling Peptides and Proteins
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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.
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