Advances in understanding the molecular basis of frontotemporal dementia (original) (raw)

• Bird, T. et al. Epidemiology and genetics of frontotemporal dementia/Pick's disease. Ann. Neurol. 54 (Suppl. 5), S29–S31 (2003).
  PubMed Google Scholar
• Feldman, H. et al. A Canadian cohort study of cognitive impairment and related dementias (ACCORD): study methods and baseline results. Neuroepidemiology 22, 265–274 (2003).
  CAS PubMed Google Scholar
• [No authors listed] Clinical and neuropathological criteria for frontotemporal dementia. The Lund and Manchester Groups. J. Neurol. Neurosurg. Psychiatry 57, 416–418 (1994).
• McKhann, G. M. et al. Clinical and pathological diagnosis of frontotemporal dementia: report of the Work Group on Frontotemporal Dementia and Pick's Disease. Arch. Neurol. 58, 1803–1809 (2001).
  CAS PubMed Google Scholar
• Neary, D. et al. Frontotemporal lobar degeneration: a consensus on clinical diagnostic criteria. Neurology 51, 1546–1554 (1998).
  CAS PubMed Google Scholar
• Burrell, J. R., Kiernan, M. C., Vucic, S. & Hodges, J. R. Motor neuron dysfunction in frontotemporal dementia. Brain 134, 2582–2594 (2011).
  PubMed Google Scholar
• Lomen-Hoerth, C., Anderson, T. & Miller, B. The overlap of amyotrophic lateral sclerosis and frontotemporal dementia. Neurology 59, 1077–1079 (2002).
  PubMed Google Scholar
• Rohrer, J. D. et al. The heritability and genetics of frontotemporal lobar degeneration. Neurology 73, 1451–1456 (2009).
  CAS PubMed PubMed Central Google Scholar
• Seelaar, H. et al. Distinct genetic forms of frontotemporal dementia. Neurology 71, 1220–1226 (2008).
  CAS PubMed Google Scholar
• Hutton, M. et al. Association of missense and 5'-splice-site mutations in tau with the inherited dementia FTDP-17. Nature 393, 702–705 (1998).
  CAS PubMed Google Scholar
• Poorkaj, P. et al. Tau is a candidate gene for chromosome 17 frontotemporal dementia. Ann. Neurol. 43, 815–825 (1998).
  CAS PubMed Google Scholar
• Spillantini, M. G. et al. Mutation in the tau gene in familial multiple system tauopathy with presenile dementia. Proc. Natl Acad. Sci. USA 95, 7737–7741 (1998).
  CAS PubMed PubMed Central Google Scholar
• Alzheimer Disease & Frontotemporal Dementia Mutation Database [online], (2012).
• Rademakers, R., Cruts, M. & van Broeckhoven, C. The role of tau (MAPT) in frontotemporal dementia and related tauopathies. Hum. Mutat. 24, 277–295 (2004).
  CAS PubMed Google Scholar
• Baker, M. et al. Mutations in progranulin cause tau-negative frontotemporal dementia linked to chromosome 17. Nature 442, 916–919 (2006).
  CAS PubMed Google Scholar
• Cruts, M. et al. Null mutations in progranulin cause ubiquitin-positive frontotemporal dementia linked to chromosome 17q21. Nature 442, 920–924 (2006).
  CAS PubMed Google Scholar
• Watts, G. D. et al. Inclusion body myopathy associated with Paget disease of bone and frontotemporal dementia is caused by mutant valosin-containing protein. Nat. Genet. 36, 377–381 (2004).
  CAS PubMed Google Scholar
• Skibinski, G. et al. Mutations in the endosomal ESCRTIII-complex subunit CHMP2B in frontotemporal dementia. Nat. Genet. 37, 806–808 (2005).
  CAS PubMed Google Scholar
• Boxer, A. L. et al. Clinical, neuroimaging and neuropathological features of a new chromosome 9p-linked FTD-ALS family. J. Neurol. Neurosurg. Psychiatr. 82, 196–203 (2011).
  Google Scholar
• Gijselinck, I. et al. Identification of 2 loci at chromosomes 9 and 14 in a multiplex family with frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Arch. Neurol. 67, 606–616 (2010).
  PubMed Google Scholar
• Le Ber, I. et al. Chromosome 9p-linked families with frontotemporal dementia associated with motor neuron disease. Neurology 72, 1669–1676 (2009).
  CAS PubMed Google Scholar
• Luty, A. A. et al. Pedigree with frontotemporal lobar degeneration—motor neuron disease and Tar DNA binding protein-43 positive neuropathology: genetic linkage to chromosome 9. BMC Neurol. 8, 32 (2008).
  PubMed PubMed Central Google Scholar
• Momeni, P. et al. Analysis of IFT74 as a candidate gene for chromosome 9p-linked ALS–FTD. BMC Neurol. 6, 44 (2006).
  PubMed PubMed Central Google Scholar
• Morita, M. et al. A locus on chromosome 9p confers susceptibility to ALS and frontotemporal dementia. Neurology 66, 839–844 (2006).
  CAS PubMed Google Scholar
• Pearson, J. P. et al. Familial frontotemporal dementia with amyotrophic lateral sclerosis and a shared haplotype on chromosome 9p. J. Neurol. 258, 647–655 (2011).
  PubMed Google Scholar
• Valdmanis, P. N. et al. Three families with amyotrophic lateral sclerosis and frontotemporal dementia with evidence of linkage to chromosome 9p. Arch. Neurol. 64, 240–245 (2007).
  PubMed Google Scholar
• Vance, C. et al. Familial amyotrophic lateral sclerosis with frontotemporal dementia is linked to a locus on chromosome 9p13.2–21.3. Brain 129, 868–876 (2006).
  PubMed Google Scholar
• DeJesus-Hernandez, M. et al. Expanded GGGGCC hexanucleotide repeat in noncoding region of C9ORF72 causes chromosome 9p-linked FTD and ALS. Neuron 72, 245–256 (2011).
  CAS PubMed PubMed Central Google Scholar
• Renton, A. E. et al. A hexanucleotide repeat expansion in C9ORF72 is the cause of chromosome 9p21-linked ALS–FTD. Neuron 72, 257–268 (2011).
  CAS PubMed PubMed Central Google Scholar
• Cairns, N. J. et al. Neuropathologic diagnostic and nosologic criteria for frontotemporal lobar degeneration: consensus of the Consortium for Frontotemporal Lobar Degeneration. Acta Neuropathol. 114, 5–22 (2007).
  PubMed PubMed Central Google Scholar
• Mackenzie, I. R. et al. Nomenclature for neuropathologic subtypes of frontotemporal lobar degeneration: consensus recommendations. Acta Neuropathol. 117, 15–18 (2009).
  PubMed Google Scholar
• Mackenzie, I. R. et al. Nomenclature and nosology for neuropathologic subtypes of frontotemporal lobar degeneration: an update. Acta Neuropathol. 119, 1–4 (2010).
  PubMed Google Scholar
• Lipton, A. M., White, C. L. 3rd & Bigio, E. H. Frontotemporal lobar degeneration with motor neuron disease-type inclusions predominates in 76 cases of frontotemporal degeneration. Acta Neuropathol. 108, 379–385 (2004).
  PubMed Google Scholar
• Mackenzie, I. R. et al. Dementia lacking distinctive histology (DLDH) revisited. Acta Neuropathol. 112, 551–559 (2006).
  PubMed Google Scholar
• Arai, T. et al. TDP-43 is a component of ubiquitin-positive tau-negative inclusions in frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Biochem. Biophys. Res. Commun. 351, 602–611 (2006).
  CAS PubMed Google Scholar
• Neumann, M. et al. Ubiquitinated TDP-43 in frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Science 314, 130–133 (2006).
  CAS PubMed Google Scholar
• Kwiatkowski, T. J. Jr et al. Mutations in the FUS/TLS gene on chromosome 16 cause familial amyotrophic lateral sclerosis. Science 323, 1205–1208 (2009).
  CAS PubMed Google Scholar
• Vance, C. et al. Mutations in FUS, an RNA processing protein, cause familial amyotrophic lateral sclerosis type 6. Science 323, 1208–1211 (2009).
  CAS PubMed PubMed Central Google Scholar
• Munoz, D. G. et al. FUS pathology in basophilic inclusion body disease. Acta Neuropathol. 118, 617–627 (2009).
  CAS PubMed Google Scholar
• Neumann, M. et al. A new subtype of frontotemporal lobar degeneration with FUS pathology. Brain 132, 2922–2931 (2009).
  PubMed PubMed Central Google Scholar
• Neumann, M. et al. Abundant FUS-immunoreactive pathology in neuronal intermediate filament inclusion disease. Acta Neuropathol. 118, 605–616 (2009).
  CAS PubMed PubMed Central Google Scholar
• Neumann, M. et al. FET proteins TAF15 and EWS are selective markers that distinguish FTLD with FUS pathology from amyotrophic lateral sclerosis with FUS mutations. Brain 134, 2595–2609 (2011).
  PubMed PubMed Central Google Scholar
• Gijselinck, I., Van Broeckhoven, C. & Cruts, M. Granulin mutations associated with frontotemporal lobar degeneration and related disorders: an update. Hum. Mutat. 29, 1373–1386 (2008).
  CAS PubMed Google Scholar
• Bateman, A. & Bennett, H. P. The granulin gene family: from cancer to dementia. Bioessays 31, 1245–1254 (2009).
  CAS PubMed Google Scholar
• Finch, N. et al. Plasma progranulin levels predict progranulin mutation status in frontotemporal dementia patients and asymptomatic family members. Brain 132, 583–591 (2009).
  PubMed PubMed Central Google Scholar
• Ghidoni, R., Benussi, L., Glionna, M., Franzoni, M. & Binetti, G. Low plasma progranulin levels predict progranulin mutations in frontotemporal lobar degeneration. Neurology 71, 1235–1239 (2008).
  CAS PubMed Google Scholar
• Sleegers, K. et al. Serum biomarker for progranulin-associated frontotemporal lobar degeneration. Ann. Neurol. 65, 603–609 (2009).
  CAS PubMed Google Scholar
• Beck, J. et al. A distinct clinical, neuropsychological and radiological phenotype is associated with progranulin gene mutations in a large UK series. Brain 131, 706–720 (2008).
  PubMed Google Scholar
• Gass, J. et al. Mutations in progranulin are a major cause of ubiquitin-positive frontotemporal lobar degeneration. Hum. Mol. Genet. 15, 2988–3001 (2006).
  CAS PubMed Google Scholar
• Le Ber, I. et al. Progranulin null mutations in both sporadic and familial frontotemporal dementia. Human. Mut. 28, 846–855 (2007).
  CAS Google Scholar
• Moreno, F. et al. “Frontotemporoparietal” dementia: clinical phenotype associated with the c.709-1G>A PGRN mutation. Neurology 73, 1367–1374 (2009).
  CAS PubMed Google Scholar
• Snowden, J. S. et al. Progranulin gene mutations associated with frontotemporal dementia and progressive non-fluent aphasia. Brain 129, 3091–3102 (2006).
  CAS PubMed Google Scholar
• Masellis, M. et al. Novel splicing mutation in the progranulin gene causing familial corticobasal syndrome. Brain 129, 3115–3123 (2006).
  PubMed Google Scholar
• Cruts, M. & Van Broeckhoven, C. Loss of progranulin function in frontotemporal lobar degeneration. Trends Genet. 24, 186–194 (2008).
  CAS PubMed Google Scholar
• Van Deerlin, V. M. et al. Common variants at 7p21 are associated with frontotemporal lobar degeneration with TDP-43 inclusions. Nat. Genet. 42, 234–239 (2010).
  CAS PubMed PubMed Central Google Scholar
• Cruchaga, C. et al. Association of TMEM106B gene polymorphism with age at onset in granulin mutation carriers and plasma granulin protein levels. Arch. Neurol. 68, 581–586 (2011).
  PubMed PubMed Central Google Scholar
• Finch, N. et al. TMEM106B regulates progranulin levels and the penetrance of FTLD in GRN mutation carriers. Neurology 76, 467–474 (2011).
  CAS PubMed Google Scholar
• van der Zee, J. et al. TMEM106B is associated with frontotemporal lobar degeneration in a clinically diagnosed patient cohort. Brain 134, 808–815 (2011).
  PubMed PubMed Central Google Scholar
• Jiao, J., Herl, L. D., Farese, R. V. & Gao, F. B. MicroRNA-29b regulates the expression level of human progranulin, a secreted glycoprotein implicated in frontotemporal dementia. PLoS ONE 5, e10551 (2010).
  PubMed PubMed Central Google Scholar
• Wang, W. X. et al. miR-107 regulates granulin/progranulin with implications for traumatic brain injury and neurodegenerative disease. Am. J. Pathol. 177, 334–345 (2010).
  CAS PubMed PubMed Central Google Scholar
• Rademakers, R. et al. Common variation in the miR-659 binding-site of GRN is a major risk factor for TDP43-positive frontotemporal dementia. Hum. Mol. Genet. 17, 3631–3642 (2008).
  CAS PubMed PubMed Central Google Scholar
• Brouwers, N. et al. Genetic variability in progranulin contributes to risk for clinically diagnosed Alzheimer disease. Neurology 71, 656–664 (2008).
  CAS PubMed Google Scholar
• Lee, M. J., Chen, T. F., Cheng, T. W. & Chiu, M. J. rs5848 variant of progranulin gene is a risk of Alzheimer's disease in the Taiwanese population. Neurodegener. Dis. 8, 216–220 (2011).
  CAS PubMed Google Scholar
• Viswanathan, J. et al. An association study between granulin gene polymorphisms and Alzheimer's disease in Finnish population. Am. J. Med. Genet. B. Neuropsychiatr. Genet. 150B, 747–750 (2009).
  CAS PubMed Google Scholar
• Cenik, B. et al. Suberoylanilide hydroxamic acid (vorinostat) up-regulates progranulin transcription: rational therapeutic approach to frontotemporal dementia. J. Biol. Chem. 286, 16101–16108 (2011).
  CAS PubMed PubMed Central Google Scholar
• Capell, A. et al. Rescue of progranulin deficiency associated with frontotemporal lobar degeneration by alkalizing reagents and inhibition of vacuolar ATPase. J. Neurosci. 31, 1885–1894 (2011).
  CAS PubMed PubMed Central Google Scholar
• Gao, X. et al. Progranulin promotes neurite outgrowth and neuronal differentiation by regulating GSK-3β. Protein Cell 1, 552–562 (2010).
  CAS PubMed PubMed Central Google Scholar
• Ryan, C. L. et al. Progranulin is expressed within motor neurons and promotes neuronal cell survival. BMC Neurosci. 10, 130 (2009).
  PubMed PubMed Central Google Scholar
• Tapia, L. et al. Progranulin deficiency decreases gross neural connectivity but enhances transmission at individual synapses. J. Neurosci. 31, 11126–11132 (2011).
  CAS PubMed PubMed Central Google Scholar
• Van Damme, P. et al. Progranulin functions as a neurotrophic factor to regulate neurite outgrowth and enhance neuronal survival. J. Cell. Biol. 181, 37–41 (2008).
  CAS PubMed PubMed Central Google Scholar
• Kleinberger, G. et al. Increased caspase activation and decreased TDP-43 solubility in progranulin knockout cortical cultures. J. Neurochem. 115, 735–747 (2010).
  CAS PubMed Google Scholar
• Nedachi, T., Kawai, T., Matsuwaki, T., Yamanouchi, K. & Nishihara, M. Progranulin enhances neural progenitor cell proliferation through glycogen synthase kinase 3β phosphorylation. Neuroscience 185, 106–115 (2011).
  CAS PubMed Google Scholar
• Rosen, E. Y. et al. Functional genomic analyses identify pathways dysregulated by progranulin deficiency, implicating Wnt signaling. Neuron 71, 1030–1042 (2011).
  CAS PubMed PubMed Central Google Scholar
• Xu, J. et al. Extracellular progranulin protects cortical neurons from toxic insults by activating survival signaling. Neurobiol. Aging 32, 2326.e5–2326.e16 (2011).
  CAS Google Scholar
• Guo, A., Tapia, L., Bamji, S. X., Cynader, M. S. & Jia, W. Progranulin deficiency leads to enhanced cell vulnerability and TDP-43 translocation in primary neuronal cultures. Brain Res. 1366, 1–8 (2010).
  CAS PubMed Google Scholar
• Carrasquillo, M. M. et al. Genome-wide screen identifies rs646776 near sortilin as a regulator of progranulin levels in human plasma. Am. J. Hum. Genet. 87, 890–897 (2010).
  CAS PubMed PubMed Central Google Scholar
• Hu, F. et al. Sortilin-mediated endocytosis determines levels of the frontotemporal dementia protein, progranulin. Neuron 68, 654–667 (2010).
  CAS PubMed PubMed Central Google Scholar
• Tang, W. et al. The growth factor progranulin binds to TNF receptors and is therapeutic against inflammatory arthritis in mice. Science 332, 478–484 (2011).
  CAS PubMed PubMed Central Google Scholar
• Boeve, B. F. et al. Characterization of frontotemporal dementia and/or amyotrophic lateral sclerosis associated with the GGGGCC repeat expansion in C9ORF72. Brain 135, 765–783 (2012).
  PubMed PubMed Central Google Scholar
• Brettschneider, J. et al. Pattern of ubiquilin pathology in ALS and FTLD indicates presence of C9ORF72 hexanucleotide expansion. Acta Neuropathol. 123, 825–839 (2012).
  PubMed PubMed Central Google Scholar
• Byrne, S. et al. Cognitive and clinical characteristics of patients with amyotrophic lateral sclerosis carrying a C9orf72 repeat expansion: a population-based cohort study. Lancet Neurol. 11, 232–240 (2012).
  CAS PubMed PubMed Central Google Scholar
• Chio, A. et al. Clinical characteristics of patients with familial amyotrophic lateral sclerosis carrying the pathogenic GGGGCC hexanucleotide repeat expansion of C9ORF72. Brain 135, 784–793 (2012).
  PubMed PubMed Central Google Scholar
• Cooper-Knock, J. et al. Clinico-pathological features in amyotrophic lateral sclerosis with expansions in C9ORF72. Brain 135, 751–764 (2012).
  PubMed PubMed Central Google Scholar
• Floris, G. et al. Frontotemporal dementia with psychosis, parkinsonism, visuo-spatial dysfunction, upper motor neuron involvement associated to expansion of C9ORF72: a peculiar phenotype? J. Neurol. http://dx.doi.org/10.1007/s00415-012-6444-3.
• Gijselinck, I. et al. 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. Lancet Neurol. 11, 54–65 (2012).
  CAS PubMed Google Scholar
• Hsiung, G. Y. et al. Clinical and pathological features of familial frontotemporal dementia caused by C9ORF72 mutation on chromosome 9p. Brain 135, 709–722 (2012).
  PubMed PubMed Central Google Scholar
• Kandiah, N. et al. Case report of an Asian patient with FTD–ALS due to C9ORF72 mutation. Can. J. Neurol. Sci. (in press).
• Mahoney, C. J. et al. Frontotemporal dementia with the C9ORF72 hexanucleotide repeat expansion: clinical, neuroanatomical and neuropathological features. Brain 135, 736–750 (2012).
  PubMed PubMed Central Google Scholar
• Majounie, E. et al. Frequency of the C9orf72 hexanucleotide repeat expansion in patients with amyotrophic lateral sclerosis and frontotemporal dementia: a cross-sectional study. Lancet Neurol. 11, 323–330 (2012).
  CAS PubMed PubMed Central Google Scholar
• Mok, K. Y. et al. High frequency of the expanded C9ORF72 hexanucleotide repeat in familial and sporadic Greek ALS patients. Neurobiol. Aging http://dx.doi.org/10.1016/j.neurobiolaging.2012.02.021.
• Murray, M. E. et al. Clinical and neuropathologic heterogeneity of c9FTD/ALS associated with hexanucleotide repeat expansion in C9ORF72. Acta Neuropathol. 122, 673–690 (2011).
  CAS PubMed PubMed Central Google Scholar
• Sabatelli, M. et al. C9ORF72 hexanucleotide repeat expansions in the Italian sporadic ALS population. Neurobiol. Aging http://dx.doi.org/10.1016/j.neurobiolaging.2012.02.011.
• Simon-Sanchez, J. et al. The clinical and pathological phenotype of C9ORF72 hexanucleotide repeat expansions. Brain 135, 723–735 (2012).
  PubMed Google Scholar
• Snowden, J. S. et al. Distinct clinical and pathological characteristics of frontotemporal dementia associated with C9ORF72 mutations. Brain 135, 693–708 (2012).
  PubMed PubMed Central Google Scholar
• Stewart, H. et al. Clinical and pathological features of amyotrophic lateral sclerosis caused by mutation in the C9ORF72 gene on chromosome 9p. Acta Neuropathol. 123, 409–417 (2012).
  CAS PubMed PubMed Central Google Scholar
• Mok, K. et al. Chromosome 9 ALS and FTD locus is probably derived from a single founder. Neurobiol. Aging 33, 209.e3–209.e8 (2012).
  CAS Google Scholar
• Rademakers, R. C9orf72 repeat expansions in patients with ALS and FTD. Lancet Neurol. 11, 297–298 (2012).
  PubMed PubMed Central Google Scholar
• Whitwell, J. L. et al. Neuroimaging signatures of frontotemporal dementia genetics: C9ORF72, tau, progranulin and sporadics. Brain 135, 794–806 (2012).
  PubMed PubMed Central Google Scholar
• Al-Sarraj, S. et al. 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. Acta Neuropathol. 122, 691–702 (2011).
  CAS PubMed Google Scholar
• Troakes, C. et al. 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. Neuropathology http://dx.doi.org/10.1111/j.1440-1789.2011.01286.x.
• Lavedan, C. et al. Myotonic dystrophy: size- and sex-dependent dynamics of CTG meiotic instability, and somatic mosaicism. Am. J. Hum. Genet. 52, 875–883 (1993).
  CAS PubMed PubMed Central Google Scholar
• Matsuura, T. et al. Somatic and germline instability of the ATTCT repeat in spinocerebellar ataxia type 10. Am. J. Hum. Genet. 74, 1216–1224 (2004).
  CAS PubMed PubMed Central Google Scholar
• Moseley, M. L. et al. SCA8 CTG repeat: en masse contractions in sperm and intergenerational sequence changes may play a role in reduced penetrance. Hum. Mol. Genet. 9, 2125–2130 (2000).
  CAS PubMed Google Scholar
• Renoux, A. J. & Todd, P. K. Neurodegeneration the RNA way. Prog. Neurobiol. 97, 173–189 (2011).
  PubMed PubMed Central Google Scholar
• Rademakers, R. et al. Mutations in the colony stimulating factor 1 receptor (CSF1R) gene cause hereditary diffuse leukoencephalopathy with spheroids. Nat. Genet. 44, 200–205 (2012).
  CAS Google Scholar
• Kabashi, E. et al. Gain and loss of function of ALS-related mutations of TARDBP (TDP-43) cause motor deficits in vivo. Hum. Mol. Genet. 19, 671–683 (2010).
  CAS PubMed Google Scholar
• Sreedharan, J. et al. TDP-43 mutations in familial and sporadic amyotrophic lateral sclerosis. Science 319, 1668–1672 (2008).
  CAS PubMed PubMed Central Google Scholar
• Deng, H. X. et al. Mutations in UBQLN2 cause dominant X-linked juvenile and adult-onset ALS and ALS/dementia. Nature 477, 211–215 (2011).
  CAS PubMed PubMed Central Google Scholar
• Buratti, E. & Baralle, F. E. The multiple roles of TDP-43 in pre-mRNA processing and gene expression regulation. RNA Biol. 7, 420–429 (2010).
  CAS PubMed Google Scholar
• Polymenidou, M. et al. Long pre-mRNA depletion and RNA missplicing contribute to neuronal vulnerability from loss of TDP-43. Nat. Neurosci. 14, 459–468 (2011).
  CAS PubMed PubMed Central Google Scholar
• Tollervey, J. R. et al. Characterizing the RNA targets and position-dependent splicing regulation by TDP-43. Nat. Neurosci. 14, 452–458 (2011).
  CAS PubMed PubMed Central Google Scholar
• Van Deerlin, V. M. et al. TARDBP mutations in amyotrophic lateral sclerosis with TDP-43 neuropathology: a genetic and histopathological analysis. Lancet Neurol. 7, 409–416 (2008).
  CAS PubMed PubMed Central Google Scholar
• Kovacs, G. G. et al. TARDBP variation associated with frontotemporal dementia, supranuclear gaze palsy, and chorea. Mov. Disord. 24, 1843–1847 (2009).
  PubMed Google Scholar
• Neumann, M. et al. TDP-43 in the ubiquitin pathology of frontotemporal dementia with VCP gene mutations. J. Neuropathol. Exp. Neurol. 66, 152–157 (2007).
  PubMed Google Scholar
• Cairns, N. J. et al. TDP-43 in familial and sporadic frontotemporal lobar degeneration with ubiquitin inclusions. Am. J. Pathol. 171, 227–240 (2007).
  CAS PubMed PubMed Central Google Scholar
• Mackenzie, I. R. et al. Heterogeneity of ubiquitin pathology in frontotemporal lobar degeneration: classification and relation to clinical phenotype. Acta Neuropathol. 112, 539–549 (2006).
  PubMed PubMed Central Google Scholar
• Mackenzie, I. R. et al. A harmonized classification system for FTLD-TDP pathology. Acta Neuropathol. 122, 111–113 (2011).
  PubMed PubMed Central Google Scholar
• Sampathu, D. M. et al. Pathological heterogeneity of frontotemporal lobar degeneration with ubiquitin-positive inclusions delineated by ubiquitin immunohistochemistry and novel monoclonal antibodies. Am. J. Pathol. 169, 1343–1352 (2006).
  CAS PubMed PubMed Central Google Scholar
• Hasegawa, M. et al. Molecular dissection of TDP-43 proteinopathies. J. Mol. Neurosci. 45, 480–485 (2011).
  CAS PubMed Google Scholar
• Lee, E. B., Lee, V. M. & Trojanowski, J. Q. Gains or losses: molecular mechanisms of TDP43-mediated neurodegeneration. Nat. Rev. Neurosci. 13, 38–50 (2012).
  CAS Google Scholar
• Mackenzie, I. R., Rademakers, R. & Neumann, M. TDP-43 and FUS in amyotrophic lateral sclerosis and frontotemporal dementia. Lancet Neurol. 9, 995–1007 (2010).
  CAS PubMed Google Scholar
• Da Cruz, S. & Cleveland, D. W. Understanding the role of TDP-43 and FUS/TLS in ALS and beyond. Curr. Opin. Neurobiol. 21, 904–919 (2011).
  CAS PubMed PubMed Central Google Scholar
• Tan, A. Y. & Manley, J. L. The TET family of proteins: functions and roles in disease. J. Mol. Cell Biol. 1, 82–92 (2009).
  CAS PubMed PubMed Central Google Scholar
• Hoell, J. I. et al. RNA targets of wild-type and mutant FET family proteins. Nat. Struct. Mol. Biol. 18, 1428–1431 (2011).
  CAS PubMed PubMed Central Google Scholar
• Urwin, H. et al. FUS pathology defines the majority of tau- and TDP-43-negative frontotemporal lobar degeneration. Acta Neuropathol. 120, 33–41 (2010).
  PubMed PubMed Central Google Scholar
• Mackenzie, I. R. et al. Pathological heterogeneity in amyotrophic lateral sclerosis with FUS mutations: two distinct patterns correlating with disease severity and mutation. Acta Neuropathol. 122, 87–98 (2011).
  PubMed PubMed Central Google Scholar
• Mackenzie, I. R. et al. Distinct pathological subtypes of FTLD-FUS. Acta Neuropathol. 121, 207–218 (2011).
  PubMed Google Scholar
• Couthouis, J. et al. A yeast functional screen predicts new candidate ALS disease genes. Proc. Natl Acad. Sci. USA 108, 20881–20890 (2011).
  CAS PubMed PubMed Central Google Scholar
• Couthouis, J. et al. Evaluating the role of the FUS/TLS-related gene EWSR1 in amyotrophic lateral sclerosis. Hum. Mol. Genet. http://dx.doi.org/10.1093/hmg/dds116.
• Ticozzi, N. et al. Mutational analysis reveals the FUS homolog TAF15 as a candidate gene for familial amyotrophic lateral sclerosis. Am. J. Med. Genet. B. Neuropsychiatr. Genet. 156, 285–290 (2011).
  CAS Google Scholar
• Dormann, D. et al. ALS-associated fused in sarcoma (FUS) mutations disrupt Transportin-mediated nuclear import. EMBO J. 29, 2841–2857 (2010).
  CAS PubMed PubMed Central Google Scholar
• Ito, D., Seki, M., Tsunoda, Y., Uchiyama, H. & Suzuki, N. Nuclear transport impairment of amyotrophic lateral sclerosis-linked mutations in FUS/TLS. Ann. Neurol. 69, 152–162 (2010).
  PubMed Google Scholar
• Belyanskaya, L. L., Delattre, O. & Gehring, H. Expression and subcellular localization of Ewing sarcoma (EWS) protein is affected by the methylation process. Exp. Cell Res. 288, 374–381 (2003).
  CAS PubMed Google Scholar
• Jobert, L., Argentini, M. & Tora, L. PRMT1 mediated methylation of TAF15 is required for its positive gene regulatory function. Exp. Cell Res. 315, 1273–1286 (2009).
  CAS PubMed Google Scholar
• Rappsilber, J., Friesen, W. J., Paushkin, S., Dreyfuss, G. & Mann, M. Detection of arginine dimethylated peptides by parallel precursor ion scanning mass spectrometry in positive ion mode. Anal. Chem. 75, 3107–3114 (2003).
  CAS PubMed Google Scholar
• Fronz, K. et al. Arginine methylation of the nuclear poly(A) binding protein weakens the interaction with its nuclear import receptor, transportin. J. Biol. Chem. 286, 32986–32994 (2011).
  CAS PubMed PubMed Central Google Scholar
• Deloulme, J. C., Prichard, L., Delattre, O. & Storm, D. R. The prooncoprotein EWS binds calmodulin and is phosphorylated by protein kinase C through an IQ domain. J. Biol. Chem. 272, 27369–27377 (1997).
  CAS PubMed Google Scholar
• Perrotti, D. et al. TLS/FUS, a pro-oncogene involved in multiple chromosomal translocations, is a novel regulator of BCR/ABL-mediated leukemogenesis. EMBO J. 17, 4442–4455 (1998).
  CAS PubMed PubMed Central Google Scholar
• Leemann-Zakaryan, R. P., Pahlich, S., Grossenbacher, D. & Gehring, H. Tyrosine phosphorylation in the C-terminal nuclear localization and retention signal (C-NLS) of the EWS protein. Sarcoma 2011, 218483 (2011).
  PubMed PubMed Central Google Scholar
• Page, T. et al. FUS immunogold labeling TEM analysis of the neuronal cytoplasmic inclusions of neuronal intermediate filament inclusion disease: a frontotemporal lobar degeneration with FUS proteinopathy. J. Mol. Neurosci. 45, 409–421 (2011).
  CAS PubMed PubMed Central Google Scholar
• Lanson, N. A. Jr & Pandey, U. B. FUS-related proteinopathies: lessons from animal models. Brain Res. http://dx.doi.org/10.1016/j.brainres.2012.01.039.
• Josephs, K. A. et al. Neuropathological background of phenotypical variability in frontotemporal dementia. Acta Neuropathol. 122, 137–153 (2011).
  PubMed PubMed Central Google Scholar
• Rohrer, J. D. & Warren, J. D. Phenotypic signatures of genetic frontotemporal dementia. Curr. Opin. Neurol. 24, 542–549 (2011).
  PubMed Google Scholar
• Hu, W. T., Trojanowski, J. Q. & Shaw, L. M. Biomarkers in frontotemporal lobar degenerations--progress and challenges. Prog. Neurobiol. 95, 636–648 (2011).
  CAS PubMed PubMed Central Google Scholar
• Noto, Y. et al. Elevated CSF TDP-43 levels in amyotrophic lateral sclerosis: specificity, sensitivity, and a possible prognostic value. Amyotroph. Lateral Scler. 12, 140–143 (2011).
  CAS PubMed Google Scholar
• Time is ripe for clinical trials in frontotemporal degeneration. Alzheimer Research Forum [online], (2011).
• Pick, A. Über die Beziehungen der senilen Hirnatrophie zur Aphasie [German]. Prager medicinische Wochenschrift 17, 165–167 (1892).
  Google Scholar
• Alzheimer, A. Über eigenartige Krankheitsfäelle des späeteren Alters [German]. Z. Gesamte Neurol. Psychiatrie 4, 356–385 (1911).
  Google Scholar
• Rebeiz, J. J., Kolodny, E. H. & Richardson, E. P. Jr. Corticodentatonigral degeneration with neuronal achromasia. Arch. Neurol. 18, 20–33 (1968).
  CAS PubMed Google Scholar
• Steele, J. C., Richardson, J. C. & Olszewski, J. Progressive supranuclear palsy. A heterogeneous degeneration involving the brain stem, basal ganglia and cerebellum with vertical gaze and pseudobulbar palsy, nuchal dystonia and dementia. Arch. Neurol. 10, 333–359 (1964).
  CAS PubMed Google Scholar
• Constantinidis, J., Richard, J. & Tissot, R. Pick's disease. Histological and clinical correlations. Eur. Neurol. 11, 208–217 (1974).
  CAS PubMed Google Scholar
• Lee, V. M., Goedert, M. & Trojanowski, J. Q. Neurodegenerative tauopathies. Annu. Rev. Neurosci. 24, 1121–1159 (2001).
  CAS PubMed Google Scholar
• Knopman, D. S., Mastri, A. R., Frey, W. H. 2nd, Sung, J. H. & Rustan, T. Dementia lacking distinctive histologic features: a common non-Alzheimer degenerative dementia. Neurology 40, 251–256 (1990).
  CAS PubMed Google Scholar
• Jackson, M., Lennox, G. & Lowe, J. Motor neurone disease-inclusion dementia. Neurodegeneration 5, 339–350 (1996).
  CAS PubMed Google Scholar
• Mackenzie, I. R., Foti, D., Woulfe, J. & Hurwitz, T. A. Atypical frontotemporal lobar degeneration with ubiquitin-positive, TDP-43-negative neuronal inclusions. Brain 131, 1282–1293 (2008).
  PubMed Google Scholar
• Roeber, S., Mackenzie, I. R., Kretzschmar, H. A. & Neumann, M. TDP-43-negative FTLD-U is a significant new clinico–pathological subtype of FTLD. Acta Neuropathol. 116, 147–157 (2008).
  CAS PubMed Google Scholar
• Laaksovirta, H. et al. Chromosome 9p21 in amyotrophic lateral sclerosis in Finland: a genome-wide association study. Lancet Neurol. 9, 978–985 (2010).
  CAS PubMed PubMed Central Google Scholar
• Shatunov, A. et al. Chromosome 9p21 in sporadic amyotrophic lateral sclerosis in the UK and seven other countries: a genome-wide association study. Lancet Neurol. 9, 986–994 (2010).
  CAS PubMed PubMed Central Google Scholar
• van Es, M. A. et al. Genome-wide association study identifies 19p13.3 (UNC13A) and 9p21.2 as susceptibility loci for sporadic amyotrophic lateral sclerosis. Nat. Genet. 41, 1083–1087 (2009).
  CAS PubMed Google Scholar