Frontotemporal lobar degeneration: defining phenotypic diversity through personalized medicine

详细信息    查看全文

• 作者：David J. Irwin (1) (2)
  Nigel J. Cairns (4)
  Murray Grossman (2)
  Corey T. McMillan (2)
  Edward B. Lee (3)
  Vivianna M. Van Deerlin (1)
  Virginia M.-Y. Lee (1)
  John Q. Trojanowski (1)
  
  1. Department of Pathology and Laboratory Medicine ; Center for Neurodegenerative Disease Research ; Institute on Ageing ; University of Pennsylvania School of Medicine ; HUP Maloney 3rd Floor ; 36th and Spruce Streets ; Philadelphia ; PA ; 19104-4283 ; USA
  2. Department of Neurology ; Penn Frontotemporal Degeneration Center ; University of Pennsylvania ; Philadelphia ; PA ; 19104 ; USA
  4. Department of Pathology and Immunology ; Washington University School of Medicine ; St. Louis ; MO ; 63110 ; USA
  3. Translational Neuropathology Research Laboratory ; Department of Pathology and Laboratory Medicine ; Perelman School of Medicine ; University of Pennsylvania ; Philadelphia ; PA ; 19104 ; USA
  
• 关键词：FTLD ; TDP ; 43 ; Tau ; ALS ; C9orf72 ; GRN ; MAPT
• 刊名：Acta Neuropathologica
• 出版年：2015
• 出版时间：April 2015
• 年：2015
• 卷：129
• 期：4
• 页码：469-491
• 全文大小：1,686 KB
• 参考文献：1. Ahmed, Z, Bigio, EH, Budka, H, Dickson, DW, Ferrer, I, Ghetti, B, Giaccone, G, Hatanpaa, KJ, Holton, JL, Josephs, KA (2013) Globular glial tauopathies (GGT): consensus recommendations. Acta Neuropathol 126: pp. 537-544
  2. Al-Sarraj, S, King, A, Troakes, C, Smith, B, Maekawa, S, Bodi, I, Rogelj, B, Al-Chalabi, A, Hortobagyi, T, Shaw, CE (2011) 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: pp. 691-702
  3. Alladi, S, Xuereb, J, Bak, T, Nestor, P, Knibb, J, Patterson, K, Hodges, JR (2007) Focal cortical presentations of Alzheimer鈥檚 disease. Brain 130: pp. 2636-2645
  4. Amador-Ortiz, C, Lin, WL, Ahmed, Z, Personett, D, Davies, P, Duara, R, Graff-Radford, NR, Hutton, ML, Dickson, DW (2007) TDP-43 immunoreactivity in hippocampal sclerosis and Alzheimer鈥檚 disease. Ann Neurol 61: pp. 435-445
  5. Arai, T, Hasegawa, M, Akiyama, H, Ikeda, K, Nonaka, T, Mori, H, Mann, D, Tsuchiya, K, Yoshida, M, Hashizume, Y (2006) TDP-43 is a component of ubiquitin-positive tau-negative inclusions in frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Biochem Biophys Res Commun 351: pp. 602-611
  6. Armstrong, MJ, Litvan, I, Lang, AE, Bak, TH, Bhatia, KP, Borroni, B, Boxer, AL, Dickson, DW, Grossman, M, Hallett, M (2013) Criteria for the diagnosis of corticobasal degeneration. Neurology 80: pp. 496-503
  7. Armstrong, R, Cairns, N, Lantos, P (1999) The spatial patterns of Pick bodies, Pick cells and Alzheimer鈥檚 disease pathology in Pick鈥檚 disease. Neuropathology 19: pp. 64-70
  8. Armstrong, RA, Cairns, NJ (2012) Different molecular pathologies result in similar spatial patterns of cellular inclusions in neurodegenerative disease: a comparative study of eight disorders. J Neural Transm 119: pp. 1551-1560
  9. Armstrong, RA, Cairns, NJ, Lantos, PL (1999) Laminar distribution of pick bodies, pick cells and Alzheimer disease pathology in the frontal and temporal cortex in Pick鈥檚 disease. Neuropathol Appl Neurobiol 25: pp. 266-271
  10. Ash, PE, Bieniek, KF, Gendron, TF, Caulfield, T, Lin, WL, Dejesus-Hernandez, M, Blitterswijk, MM, Jansen-West, K, Paul, JW, Rademakers, R (2013) Unconventional translation of C9ORF72 GGGGCC expansion generates insoluble polypeptides specific to c9FTD/ALS. Neuron 77: pp. 639-646
  11. Baborie A, Griffiths TD, Jaros E, Perry R, McKeith IG, Burn DJ, Masuda-Suzukake M, Hasegawa M, Rollinson S, Pickering-Brown Set al (2014) Accumulation of dipeptide repeat proteins predates that of TDP-43 in Frontotemporal Lobar Degeneration associated with hexanucleotide repeat expansions in C9ORF72 gene. Neuropathol Appl Neurobiol. doi:10.1111/nan.12178
  12. Baker, M, Litvan, I, Houlden, H, Adamson, J, Dickson, D, Perez-Tur, J, Hardy, J, Lynch, T, Bigio, E, Hutton, M (1999) Association of an extended haplotype in the tau gene with progressive supranuclear palsy. Hum Mol Genet 8: pp. 711-715
  13. Baker, M, Mackenzie, IR, Pickering-Brown, SM, Gass, J, Rademakers, R, Lindholm, C, Snowden, J, Adamson, J, Sadovnick, AD, Rollinson, S (2006) Mutations in progranulin cause tau-negative frontotemporal dementia linked to chromosome 17. Nature 442: pp. 916-919
  14. Beck, J, Poulter, M, Hensman, D, Rohrer, JD, Mahoney, CJ, Adamson, G, Campbell, T, Uphill, J, Borg, A, Fratta, P (2013) Large C9orf72 hexanucleotide repeat expansions are seen in multiple neurodegenerative syndromes and are more frequent than expected in the UK population. Am J Hum Genet 92: pp. 345-353
  15. Behrens, MI, Mukherjee, O, Tu, PH, Liscic, RM, Grinberg, LT, Carter, D, Paulsmeyer, K, Taylor-Reinwald, L, Gitcho, M, Norton, JB (2007) Neuropathologic heterogeneity in HDDD1: a familial frontotemporal lobar degeneration with ubiquitin-positive inclusions and progranulin mutation. Alzheimer Dis Assoc Disord 21: pp. 1-7
  16. Bell, K, Cairns, NJ, Lantos, PL, Rossor, MN (2000) Immunohistochemistry distinguishes: between Pick鈥檚 disease and corticobasal degeneration. J Neurol Neurosurg Psychiatry 69: pp. 835-836
  17. Berry, RW, Sweet, AP, Clark, FA, Lagalwar, S, Lapin, BR, Wang, T, Topgi, S, Guillozet-Bongaarts, AL, Cochran, EJ, Bigio, EH (2004) Tau epitope display in progressive supranuclear palsy and corticobasal degeneration. J Neurocytol 33: pp. 287-295
  18. Bhardwaj, A, Myers, MP, Buratti, E, Baralle, FE (2013) Characterizing TDP-43 interaction with its RNA targets. Nucleic Acids Res 41: pp. 5062-5074
  19. Bian, H, Swieten, JC, Leight, S, Massimo, L, Wood, E, Forman, M, Moore, P, Koning, I, Clark, CM, Rosso, S (2008) CSF biomarkers in frontotemporal lobar degeneration with known pathology. Neurology 70: pp. 1827-1835
  20. Bieniek, KF, Blitterswijk, M, Baker, MC, Petrucelli, L, Rademakers, R, Dickson, DW (2014) Expanded C9ORF72 hexanucleotide repeat in depressive pseudodementia. JAMA Neurol 71: pp. 775-781
  21. Bigio, EH, Wu, JY, Deng, HX, Bit-Ivan, EN, Mao, Q, Ganti, R, Peterson, M, Siddique, N, Geula, C, Siddique, T (2013) Inclusions in frontotemporal lobar degeneration with TDP-43 proteinopathy (FTLD-TDP) and amyotrophic lateral sclerosis (ALS), but not FTLD with FUS proteinopathy (FTLD-FUS), have properties of amyloid. Acta Neuropathol 125: pp. 463-465
  22. Boeve, BF, Boylan, KB, Graff-Radford, NR, DeJesus-Hernandez, M, Knopman, DS, Pedraza, O, Vemuri, P, Jones, D, Lowe, V, Murray, ME (2012) Characterization of frontotemporal dementia and/or amyotrophic lateral sclerosis associated with the GGGGCC repeat expansion in C9ORF72. Brain 135: pp. 765-783
  23. Borroni, B, Gardoni, F, Parnetti, L, Magno, L, Malinverno, M, Saggese, E, Calabresi, P, Spillantini, MG, Padovani, A, Luca, M (2009) Pattern of Tau forms in CSF is altered in progressive supranuclear palsy. Neurobiol Aging 30: pp. 34-40
  24. Borroni, B, Malinverno, M, Gardoni, F, Alberici, A, Parnetti, L, Premi, E, Bonuccelli, U, Grassi, M, Perani, D, Calabresi, P (2008) Tau forms in CSF as a reliable biomarker for progressive supranuclear palsy. Neurology 71: pp. 1796-1803
  25. Boxer, AL, Gold, M, Huey, E, Gao, FB, Burton, EA, Chow, T, Kao, A, Leavitt, BR, Lamb, B, Grether, M (2012) Frontotemporal degeneration, the next therapeutic frontier: molecules and animal models for frontotemporal degeneration drug development. Alzheimer鈥檚 Dement J Alzheimer鈥檚 Assoc.
  26. Boxer, AL, Gold, M, Huey, E, Hu, WT, Rosen, H, Kramer, J, Gao, FB, Burton, EA, Chow, T, Kao, A (2012) The advantages of frontotemporal degeneration drug development (part 2 of frontotemporal degeneration: the next therapeutic frontier). Alzheimer鈥檚 Dement J Alzheimer鈥檚 Assoc.
  27. Boxer, AL, Knopman, DS, Kaufer, DI, Grossman, M, Onyike, C, Graf-Radford, N, Mendez, M, Kerwin, D, Lerner, A, Wu, CK (2013) Memantine in patients with frontotemporal lobar degeneration: a multicentre, randomised, double-blind, placebo-controlled trial. Lancet Neurol 12: pp. 149-156
  28. Boxer, AL, Lang, AE, Grossman, M, Knopman, DS, Miller, BL, Schneider, LS, Doody, RS, Lees, A, Golbe, LI, Williams, DR (2014) Davunetide in patients with progressive supranuclear palsy: a randomised, double-blind, placebo-controlled phase 2/3 trial. Lancet Neurol 13: pp. 676-685
  29. Braak, H, Braak, E (1991) Neuropathological stageing of Alzheimer-related changes. Acta Neuropathol 82: pp. 239-259
  30. Braak, H, Brettschneider, J, Ludolph, AC, Lee, VM, Trojanowski, JQ, Tredici, K (2013) Amyotrophic lateral sclerosis鈥攁 model of corticofugal axonal spread. Nat Rev Neurol 9: pp. 708-714
  31. Braak H, Del Tredici K (2014) Are cases with tau pathology occurring in the absence of Abeta deposits part of the AD-related pathological process? Acta Neuropathol. doi:10.1007/s00401-014-1356-1
  32. Bramblett, GT, Goedert, M, Jakes, R, Merrick, SE, Trojanowski, JQ, Lee, VM (1993) Abnormal tau phosphorylation at Ser396 in Alzheimer鈥檚 disease recapitulates development and contributes to reduced microtubule binding. Neuron 10: pp. 1089-1099
  33. Brettschneider, J, Tredici, K, Irwin, DJ, Grossman, M, Robinson, JL, Toledo, JB, Fang, L, Deerlin, VM, Ludolph, AC, Lee, VM (2014) Sequential distribution of pTDP-43 pathology in behavioral variant frontotemporal dementia (bvFTD). Acta Neuropathol 127: pp. 423-439
  34. Brettschneider J, Del Tredici K, Toledo JB, Robinson JL, Irwin DJ, Grossman M, Suh E, Van Deerlin VM, Wood EM, Baek Yet al (2013) Stages of pTDP-43 pathology in amyotrophic lateral sclerosis. Ann Neurol. doi:10.1002/ana.23937
  35. Brettschneider J, Tredici KD, Toledo JB, Robinson JL, Irwin DJ, Grossman M, Suh E, Van Deerlin VM, Wood EM, Baek Yet al (2013) Stages of pTDP-43 pathology in amyotrophic lateral sclerosis. Ann Neurol. doi:10.1002/ana.23937
  36. Brettschneider, J, Deerlin, VM, Robinson, JL, Kwong, L, Lee, EB, Ali, YO, Safren, N, Monteiro, MJ, Toledo, JB, Elman, L (2012) Pattern of ubiquilin pathology in ALS and FTLD indicates presence of C9ORF72 hexanucleotide expansion. Acta Neuropathol 123: pp. 825-839
  37. Brunden, KR, Trojanowski, JQ, Smith, AB, Lee, VM, Ballatore, C (2014) Microtubule-stabilizing agents as potential therapeutics for neurodegenerative disease. Bioorg Med Chem 22: pp. 5040-5049
  38. Buratti, E, Baralle, FE (2001) Characterization and functional implications of the RNA binding properties of nuclear factor TDP-43, a novel splicing regulator of CFTR exon 9. J Biol Chem 276: pp. 36337-36343
  39. Byrne, S, Elamin, M, Bede, P, Shatunov, A, Walsh, C, Corr, B, Heverin, M, Jordan, N, Kenna, K, Lynch, C (2012) Cognitive and clinical characteristics of patients with amyotrophic lateral sclerosis carrying a C9orf72 repeat expansion: a population-based cohort study. Lancet Neurol 11: pp. 232-240
  40. Cairns, NJ, Bigio, EH, Mackenzie, IR, Neumann, M, Lee, VM, Hatanpaa, KJ, White, CL, Schneider, JA, Grinberg, LT, Halliday, G (2007) Neuropathologic diagnostic and nosologic criteria for frontotemporal lobar degeneration: consensus of the Consortium for Frontotemporal Lobar Degeneration. Acta Neuropathol 114: pp. 5-22
  41. Cairns, NJ, Neumann, M, Bigio, EH, Holm, IE, Troost, D, Hatanpaa, KJ, Foong, C, White, CL, Schneider, JA, Kretzschmar, HA (2007) TDP-43 in familial and sporadic frontotemporal lobar degeneration with ubiquitin inclusions. Am J Pathol 171: pp. 227-240
  42. Cairns, NJ, Perrin, RJ, Schmidt, RE, Gru, A, Green, KG, Carter, D, Taylor-Reinwald, L, Morris, JC, Gitcho, MA, Baloh, RH (2010) TDP-43 proteinopathy in familial motor neurone disease with TARDBP A315T mutation: a case report. Neuropathol Appl Neurobiol 36: pp. 673-679
  43. Chen-Plotkin, AS, Martinez-Lage, M, Sleiman, PM, Hu, W, Greene, R, Wood, EM, Bing, S, Grossman, M, Schellenberg, GD, Hatanpaa, KJ (2011) Genetic and clinical features of progranulin-associated frontotemporal lobar degeneration. Arch Neurol 68: pp. 488-497
  44. Chen-Plotkin, AS, Unger, TL, Gallagher, MD, Bill, E, Kwong, LK, Volpicelli-Daley, L, Busch, JI, Akle, S, Grossman, M, Deerlin, V (2012) TMEM106B, the risk gene for frontotemporal dementia, is regulated by the microRNA-132/212 cluster and affects progranulin pathways. J Neurosci 32: pp. 11213-11227
  45. Chen-Plotkin, AS, Xiao, J, Geser, F, Martinez-Lage, M, Grossman, M, Unger, T, Wood, EM, Deerlin, VM, Trojanowski, JQ, Lee, VM (2010) Brain progranulin expression in GRN-associated frontotemporal lobar degeneration. Acta Neuropathol 119: pp. 111-122
  46. Chien, DT, Szardenings, AK, Bahri, S, Walsh, JC, Mu, F, Xia, C, Shankle, WR, Lerner, AJ, Su, MY, Elizarov, A (2014) Early clinical PET imaging results with the novel PHF-tau radioligand [F18]-T808. J Alzheimer鈥檚 Dis 38: pp. 171-184
  47. Clark, CM, Pontecorvo, MJ, Beach, TG, Bedell, BJ, Coleman, RE, Doraiswamy, PM, Fleisher, AS, Reiman, EM, Sabbagh, MN, Sadowsky, CH (2012) Cerebral PET with florbetapir compared with neuropathology at autopsy for detection of neuritic amyloid-beta plaques: a prospective cohort study. Lancet Neurol 11: pp. 669-678
  48. Clavaguera, F, Akatsu, H, Fraser, G, Crowther, RA, Frank, S, Hench, J, Probst, A, Winkler, DT, Reichwald, J, Staufenbiel, M (2013) Brain homogenates from human tauopathies induce tau inclusions in mouse brain. Proc Natl Acad Sci USA 110: pp. 9535-9540
  49. Cohen, TJ, Guo, JL, Hurtado, DE, Kwong, LK, Mills, IP, Trojanowski, JQ, Lee, VM (2011) The acetylation of tau inhibits its function and promotes pathological tau aggregation. Nat Commun 2: pp. 252
  50. Cook, C, Carlomagno, Y, Gendron, TF, Dunmore, J, Scheffel, K, Stetler, C, Davis, M, Dickson, D, Jarpe, M, DeTure, M (2014) Acetylation of the KXGS motifs in tau is a critical determinant in modulation of tau aggregation and clearance. Hum Mol Genet 23: pp. 104-116
  51. Crary JF, Trojanowski JQ, Schneider JA, Abisambra JF, Abner EL, Alafuzoff I, Arnold SE, Attems J, Beach TG, Bigio EHet al (2014) Primary age-related tauopathy (PART): a common pathology associated with human aging. Acta Neuropathol. doi:10.1007/s00401-014-1349-0
  52. Cruchaga, C, Graff, C, Chiang, HH, Wang, J, Hinrichs, AL, Spiegel, N, Bertelsen, S, Mayo, K, Norton, JB, Morris, JC (2011) Association of TMEM106B gene polymorphism with age at onset in granulin mutation carriers and plasma granulin protein levels. Arch Neurol 68: pp. 581-586
  53. Cruts, M, Gijselinck, I, Zee, J, Engelborghs, S, Wils, H, Pirici, D, Rademakers, R, Vandenberghe, R, Dermaut, B, Martin, JJ (2006) Null mutations in progranulin cause ubiquitin-positive frontotemporal dementia linked to chromosome 17q21. Nature 442: pp. 920-924
  54. Dai, RM, Li, CC (2001) Valosin-containing protein is a multi-ubiquitin chain-targeting factor required in ubiquitin鈥損roteasome degradation. Nat Cell Biol 3: pp. 740-744
  55. DeJesus-Hernandez, M, Mackenzie, IR, Boeve, BF, Boxer, AL, Baker, M, Rutherford, NJ, Nicholson, AM, Finch, NA, Flynn, H, Adamson, J (2011) Expanded GGGGCC hexanucleotide repeat in noncoding region of C9ORF72 causes chromosome 9p-linked FTD and ALS. Neuron 72: pp. 245-256
  56. Delacourte, A, Robitaille, Y, Sergeant, N, Buee, L, Hof, PR, Wattez, A, Laroche-Cholette, A, Mathieu, J, Chagnon, P, Gauvreau, D (1996) Specific pathological Tau protein variants characterize Pick鈥檚 disease. J Neuropathol Exp Neurol 55: pp. 159-168
  57. Dickson, DW, Kouri, N, Murray, ME, Josephs, KA (2011) Neuropathology of frontotemporal lobar degeneration-tau (FTLD-tau). J Mol Neurosci 45: pp. 384-389
  58. Dopper, EG, Rombouts, SA, Jiskoot, LC, Heijer, T, Graaf, JR, Koning, I, Hammerschlag, AR, Seelaar, H, Seeley, WW, Veer, IM (2014) Structural and functional brain connectivity in presymptomatic familial frontotemporal dementia. Neurology 83: pp. e19-e26
  59. Ferrari, R, Hernandez, DG, Nalls, MA, Rohrer, JD, Ramasamy, A, Kwok, JB, Dobson-Stone, C, Brooks, WS, Schofield, PR, Halliday, GM (2014) Frontotemporal dementia and its subtypes: a genome-wide association study. Lancet Neurol 13: pp. 686-699
  60. Ferrer, I, Santpere, G, Leeuwen, FW (2008) Argyrophilic grain disease. Brain 131: pp. 1416-1432
  61. Finch, N, Baker, M, Crook, R, Swanson, K, Kuntz, K, Surtees, R, Bisceglio, G, Rovelet-Lecrux, A, Boeve, B, Petersen, RC (2009) Plasma progranulin levels predict progranulin mutation status in frontotemporal dementia patients and asymptomatic family members. Brain 132: pp. 583-591
  62. Finch, N, Carrasquillo, MM, Baker, M, Rutherford, NJ, Coppola, G, Dejesus-Hernandez, M, Crook, R, Hunter, T, Ghidoni, R, Benussi, L (2011) TMEM106B regulates progranulin levels and the penetrance of FTLD in GRN mutation carriers. Neurology 76: pp. 467-474
  63. Forman M, Trojanoswki JQ, Lee VM-Y (2004) Hereditary tauopathies and idiopathic frontotemporal dementias. Cambridge University Press, London
  64. Forman, MS, Farmer, J, Johnson, JK, Clark, CM, Arnold, SE, Coslett, HB, Chatterjee, A, Hurtig, HI, Karlawish, JH, Rosen, HJ (2006) Frontotemporal dementia: clinicopathological correlations. Ann Neurol 59: pp. 952-962
  65. Forman, MS, Zhukareva, V, Bergeron, C, Chin, SS, Grossman, M, Clark, C, Lee, VM, Trojanowski, JQ (2002) Signature tau neuropathology in gray and white matter of corticobasal degeneration. Am J Pathol 160: pp. 2045-2053
  66. Foulds, P, McAuley, E, Gibbons, L, Davidson, Y, Pickering-Brown, SM, Neary, D, Snowden, JS, Allsop, D, Mann, DM (2008) TDP-43 protein in plasma may index TDP-43 brain pathology in Alzheimer鈥檚 disease and frontotemporal lobar degeneration. Acta Neuropathol 116: pp. 141-146
  67. Freeman, SH, Spires-Jones, T, Hyman, BT, Growdon, JH, Frosch, MP (2008) TAR-DNA binding protein 43 in Pick disease. J Neuropathol Exp Neurol 67: pp. 62-67
  68. Fujishiro, H, Uchikado, H, Arai, T, Hasegawa, M, Akiyama, H, Yokota, O, Tsuchiya, K, Togo, T, Iseki, E, Hirayasu, Y (2009) Accumulation of phosphorylated TDP-43 in brains of patients with argyrophilic grain disease. Acta Neuropathol 117: pp. 151-158
  69. Gallagher, MD, Suh, E, Grossman, M, Elman, L, McCluskey, L, Swieten, JC, Al-Sarraj, S, Neumann, M, Gelpi, E, Ghetti, B (2014) TMEM106B is a genetic modifier of frontotemporal lobar degeneration with C9orf72 hexanucleotide repeat expansions. Acta Neuropathol 127: pp. 407-418
  70. Gendron, TF, Bieniek, KF, Zhang, YJ, Jansen-West, K, Ash, PE, Caulfield, T, Daughrity, L, Dunmore, JH, Castanedes-Casey, M, Chew, J (2013) Antisense transcripts of the expanded C9ORF72 hexanucleotide repeat form nuclear RNA foci and undergo repeat-associated non-ATG translation in c9FTD/ALS. Acta Neuropathol 126: pp. 829-844
  71. Geser, F, Martinez-Lage, M, Robinson, J, Uryu, K, Neumann, M, Brandmeir, NJ, Xie, SX, Kwong, LK, Elman, L, McCluskey, L (2009) Clinical and pathological continuum of multisystem TDP-43 proteinopathies. Arch Neurol 66: pp. 180-189
  72. Geser, F, Winton, MJ, Kwong, LK, Xu, Y, Xie, SX, Igaz, LM, Garruto, RM, Perl, DP, Galasko, D, Lee, VM (2008) Pathological TDP-43 in parkinsonism-dementia complex and amyotrophic lateral sclerosis of Guam. Acta Neuropathol 115: pp. 133-145
  73. Gitcho, MA, Baloh, RH, Chakraverty, S, Mayo, K, Norton, JB, Levitch, D, Hatanpaa, KJ, White, CL, Bigio, EH, Caselli, R (2008) TDP-43 A315T mutation in familial motor neuron disease. Ann Neurol 63: pp. 535-538
  74. Goldman, JS, Quinzii, C, Dunning-Broadbent, J, Waters, C, Mitsumoto, H, Brannagan, TH, Cosentino, S, Huey, ED, Nagy, P, Kuo, SH (2014) Multiple system atrophy and amyotrophic lateral sclerosis in a family with hexanucleotide repeat expansions in C9orf72. JAMA Neurol 71: pp. 771-774
  75. Gorno-Tempini, ML, Hillis, AE, Weintraub, S, Kertesz, A, Mendez, M, Cappa, SF, Ogar, JM, Rohrer, JD, Black, S, Boeve, BF (2011) Classification of primary progressive aphasia and its variants. Neurology 76: pp. 1006-1014
  76. Grinberg, LT, Wang, X, Wang, C, Sohn, PD, Theofilas, P, Sidhu, M, Arevalo, JB, Heinsen, H, Huang, EJ, Rosen, H (2013) Argyrophilic grain disease differs from other tauopathies by lacking tau acetylation. Acta Neuropathol 125: pp. 581-593
  77. Grossman, M (2011) Biomarkers to identify the pathological basis for frontotemporal lobar degeneration. J Mol Neurosci 45: pp. 366-371
  78. Grossman, M (2010) Primary progressive aphasia: clinicopathological correlations. Nat Rev Neurol 6: pp. 88-97
  79. Grossman, M, Elman, L, McCluskey, L, McMillan, CT, Boller, A, Powers, J, Rascovsky, K, Hu, W, Shaw, L, Irwin, DJ (2014) Phosphorylated tau as a candidate biomarker for amyotrophic lateral sclerosis. JAMA Neurol 71: pp. 442-448
  80. Grossman, M, Farmer, J, Leight, S, Work, M, Moore, P, Deerlin, V, Pratico, D, Clark, CM, Coslett, HB, Chatterjee, A (2005) Cerebrospinal fluid profile in frontotemporal dementia and Alzheimer鈥檚 disease. Ann Neurol 57: pp. 721-729
  81. Guillozet-Bongaarts, AL, Garcia-Sierra, F, Reynolds, MR, Horowitz, PM, Fu, Y, Wang, T, Cahill, ME, Bigio, EH, Berry, RW, Binder, LI (2005) Tau truncation during neurofibrillary tangle evolution in Alzheimer鈥檚 disease. Neurobiol Aging 26: pp. 1015-1022
  82. Guillozet-Bongaarts, AL, Glajch, KE, Libson, EG, Cahill, ME, Bigio, E, Berry, RW, Binder, LI (2007) Phosphorylation and cleavage of tau in non-AD tauopathies. Acta Neuropathol 113: pp. 513-520
  83. Guo, JL, Lee, VM (2014) Cell-to-cell transmission of pathogenic proteins in neurodegenerative diseases. Nat Med 20: pp. 130-138
  84. Guo, JL, Lee, VM (2013) Neurofibrillary tangle-like tau pathology induced by synthetic tau fibrils in primary neurons over-expressing mutant tau. FEBS Lett 587: pp. 717-723
  85. Harms, M, Benitez, BA, Cairns, N, Cooper, B, Cooper, P, Mayo, K, Carrell, D, Faber, K, Williamson, J, Bird, T (2013) C9orf72 hexanucleotide repeat expansions in clinical Alzheimer disease. JAMA Neurol 70: pp. 736-741
  86. Hart, MP, Brettschneider, J, Lee, VM, Trojanowski, JQ, Gitler, AD (2012) Distinct TDP-43 pathology in ALS patients with ataxin 2 intermediate-length polyQ expansions. Acta Neuropathol 124: pp. 221-230
  87. Hensman Moss, DJ, Poulter, M, Beck, J, Hehir, J, Polke, JM, Campbell, T, Adamson, G, Mudanohwo, E, McColgan, P, Haworth, A (2014) C9orf72 expansions are the most common genetic cause of Huntington disease phenocopies. Neurology 82: pp. 292-299
  88. Hodges, JR, Davies, RR, Xuereb, JH, Casey, B, Broe, M, Bak, TH, Kril, JJ, Halliday, GM (2004) Clinicopathological correlates in frontotemporal dementia. Ann Neurol 56: pp. 399-406
  89. Hoglinger, GU, Melhem, NM, Dickson, DW, Sleiman, PM, Wang, LS, Klei, L, Rademakers, R, Silva, R, Litvan, I, Riley, DE (2011) Identification of common variants influencing risk of the tauopathy progressive supranuclear palsy. Nat Genet 43: pp. 699-705
  90. Hong, M, Zhukareva, V, Vogelsberg-Ragaglia, V, Wszolek, Z, Reed, L, Miller, BI, Geschwind, DH, Bird, TD, McKeel, D, Goate, A (1998) Mutation-specific functional impairments in distinct tau isoforms of hereditary FTDP-17. Science 282: pp. 1914-1917
  91. Horiguchi, T, Uryu, K, Giasson, BI, Ischiropoulos, H, LightFoot, R, Bellmann, C, Richter-Landsberg, C, Lee, VM, Trojanowski, JQ (2003) Nitration of tau protein is linked to neurodegeneration in tauopathies. Am J Pathol 163: pp. 1021-1031
  92. Houlden, H, Baker, M, Morris, HR, MacDonald, N, Pickering-Brown, S, Adamson, J, Lees, AJ, Rossor, MN, Quinn, NP, Kertesz, A (2001) Corticobasal degeneration and progressive supranuclear palsy share a common tau haplotype. Neurology 56: pp. 1702-1706
  93. Hsiung, GY, DeJesus-Hernandez, M, Feldman, HH, Sengdy, P, Bouchard-Kerr, P, Dwosh, E, Butler, R, Leung, B, Fok, A, Rutherford, NJ (2012) Clinical and pathological features of familial frontotemporal dementia caused by C9ORF72 mutation on chromosome 9p. Brain 135: pp. 709-722
  94. Hu, WT, Chen-Plotkin, A, Grossman, M, Arnold, SE, Clark, CM, Shaw, LM, McCluskey, L, Elman, L, Hurtig, HI, Siderowf, A (2010) Novel CSF biomarkers for frontotemporal lobar degenerations. Neurology 75: pp. 2079-2086
  95. Hu, WT, McMillan, C, Libon, D, Leight, S, Forman, M, Lee, VM, Trojanowski, JQ, Grossman, M (2010) Multimodal predictors for Alzheimer disease in nonfluent primary progressive aphasia. Neurology 75: pp. 595-602
  96. Hu, WT, Seelaar, H, Josephs, KA, Knopman, DS, Boeve, BF, Sorenson, EJ, McCluskey, L, Elman, L, Schelhaas, HJ, Parisi, JE (2009) Survival profiles of patients with frontotemporal dementia and motor neuron disease. Arch Neurol 66: pp. 1359-1364
  97. Hu WT, Watts K, Grossman M, Glass J, Lah JJ, Hales C, Shelnutt M, Van Deerlin V, Trojanoswki JQ, Levey AI (2013) Reduced CSF p-Tau181 to Tau ratio is a biomarker for FTLD-TDP. Neurology (in press)
  98. Iba, M, Guo, JL, McBride, JD, Zhang, B, Trojanowski, JQ, Lee, VM (2013) Synthetic tau fibrils mediate transmission of neurofibrillary tangles in a transgenic mouse model of Alzheimer鈥檚-like tauopathy. J Neurosci 33: pp. 1024-1037
  99. Igaz, LM, Kwong, LK, Xu, Y, Truax, AC, Uryu, K, Neumann, M, Clark, CM, Elman, LB, Miller, BL, Grossman, M (2008) Enrichment of C-terminal fragments in TAR DNA-binding protein-43 cytoplasmic inclusions in brain but not in spinal cord of frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Am J Pathol 173: pp. 182-194
  100. Irwin, DJ, Abrams, JY, Schonberger, LB, Leschek, EW, Mills, JL, Lee, VM, Trojanowski, JQ (2013) Evaluation of potential infectivity of Alzheimer and Parkinson disease proteins in recipients of cadaver-derived human growth hormone. JAMA Neurol 70: pp. 462-468
  101. Irwin, DJ, Cohen, TJ, Grossman, M, Arnold, SE, McCarty-Wood, E, Deerlin, VM, Lee, VM, Trojanowski, JQ (2013) Acetylated tau neuropathology in sporadic and hereditary tauopathies. Am J Pathol 183: pp. 344-351
  102. Irwin, DJ, Cohen, TJ, Grossman, M, Arnold, SE, Xie, SX, Lee, VM, Trojanowski, JQ (2012) Acetylated tau, a novel pathological signature in Alzheimer鈥檚 disease and other tauopathies. Brain 135: pp. 807-818
  103. Irwin, DJ, McMillan, CT, Brettschneider, J, Libon, DJ, Powers, J, Rascovsky, K, Toledo, JB, Boller, A, Bekisz, J, Chandrasekaran, K (2013) Cognitive decline and reduced survival in C9orf72 expansion frontotemporal degeneration and amyotrophic lateral sclerosis. J Neurol Neurosurg Psychiatry 84: pp. 163-169
  104. Irwin, DJ, McMillan, CT, Suh, E, Powers, J, Rascovsky, K, Wood, EM, Toledo, JB, Arnold, SE, Lee, VM, Deerlin, VM (2014) Myelin oligodendrocyte basic protein and prognosis in behavioral-variant frontotemporal dementia. Neurology 83: pp. 502-509
  105. Irwin, DJ, McMillan, CT, Toledo, JB, Arnold, SE, Shaw, LM, Wang, LS, Deerlin, V, Lee, VM, Trojanowski, JQ, Grossman, M (2012) Comparison of cerebrospinal fluid levels of tau and Abeta 1-42 in Alzheimer disease and frontotemporal degeneration using 2 analytical platforms. Arch Neurol 69: pp. 1018-1025
  106. Irwin, DJ, Trojanowski, JQ, Grossman, M (2013) Cerebrospinal fluid biomarkers for differentiation of frontotemporal lobar degeneration from Alzheimer鈥檚 disease. Front Aging Neurosci 5: pp. 6
  107. Jellinger, KA, Attems, J (2007) Neurofibrillary tangle-predominant dementia: comparison with classical Alzheimer disease. Acta Neuropathol 113: pp. 107-117
  108. Johnson, JO, Mandrioli, J, Benatar, M, Abramzon, Y, Deerlin, VM, Trojanowski, JQ, Gibbs, JR, Brunetti, M, Gronka, S, Wuu, J (2010) Exome sequencing reveals VCP mutations as a cause of familial ALS. Neuron 68: pp. 857-864
  109. Josephs, KA, Duffy, JR, Strand, EA, Whitwell, JL, Layton, KF, Parisi, JE, Hauser, MF, Witte, RJ, Boeve, BF, Knopman, DS (2006) Clinicopathological and imaging correlates of progressive aphasia and apraxia of speech. Brain 129: pp. 1385-1398
  110. Josephs, KA, Murray, ME, Whitwell, JL, Parisi, JE, Petrucelli, L, Jack, CR, Petersen, RC, Dickson, DW (2014) Staging TDP-43 pathology in Alzheimer鈥檚 disease. Acta Neuropathol 127: pp. 441-450
  111. Josephs, KA, Whitwell, JL, Weigand, SD, Murray, ME, Tosakulwong, N, Liesinger, AM, Petrucelli, L, Senjem, ML, Knopman, DS, Boeve, BF (2014) TDP-43 is a key player in the clinical features associated with Alzheimer鈥檚 disease. Acta Neuropathol 127: pp. 811-824
  112. Jucker, M, Walker, LC (2013) Self-propagation of pathogenic protein aggregates in neurodegenerative diseases. Nature 501: pp. 45-51
  113. Kabashi, E, Valdmanis, PN, Dion, P, Spiegelman, D, McConkey, BJ, Vande Velde, C, Bouchard, JP, Lacomblez, L, Pochigaeva, K, Salachas, F (2008) TARDBP mutations in individuals with sporadic and familial amyotrophic lateral sclerosis. Nat Genet 40: pp. 572-574
  114. Kalkonde, YV, Jawaid, A, Qureshi, SU, Shirani, P, Wheaton, M, Pinto-Patarroyo, GP, Schulz, PE (2012) Medical and environmental risk factors associated with frontotemporal dementia: a case鈥揷ontrol study in a veteran population. Alzheimer鈥檚 Dement J Alzheimer鈥檚 Assoc 8: pp. 204-210
  115. Kamada, M, Izumi, Y, Ayaki, T, Nakamura, M, Kagawa, S, Kudo, E, Sako, W, Maruyama, H, Nishida, Y, Kawakami, H (2014) Clinicopathologic features of autosomal recessive amyotrophic lateral sclerosis associated with optineurin mutation. Neuropathology 34: pp. 64-70
  116. Kang, JH, Korecka, M, Toledo, JB, Trojanowski, JQ, Shaw, LM (2013) Clinical utility and analytical challenges in measurement of cerebrospinal fluid amyloid-beta(1鈥?2) and tau proteins as Alzheimer disease biomarkers. Clin Chem 59: pp. 903-916
  117. Khan, BK, Yokoyama, JS, Takada, LT, Sha, SJ, Rutherford, NJ, Fong, JC, Karydas, AM, Wu, T, Ketelle, RS, Baker, MC (2012) Atypical, slowly progressive behavioural variant frontotemporal dementia associated with C9ORF72 hexanucleotide expansion. J Neurol Neurosurg Psychiatry 83: pp. 358-364
  118. Kipps, CM, Hodges, JR, Hornberger, M (2010) Nonprogressive behavioural frontotemporal dementia: recent developments and clinical implications of the 鈥榖vFTD phenocopy syndrome鈥? Curr Opin Neurol 23: pp. 628-632
  119. Kirby, J, Highley, JR, Cox, L, Goodall, EF, Hewitt, C, Hartley, JA, Hollinger, HC, Fox, M, Ince, PG, McDermott, CJ (2013) Lack of unique neuropathology in amyotrophic lateral sclerosis associated with p.K54E angiogenin (ANG) mutation. Neuropathol Appl Neurobiol 39: pp. 562-571
  120. Knibb, JA, Xuereb, JH, Patterson, K, Hodges, JR (2006) Clinical and pathological characterization of progressive aphasia. Ann Neurol 59: pp. 156-165
  121. Knopman, DS (1993) Overview of dementia lacking distinctive histology: pathological designation of a progressive dementia. Dementia 4: pp. 132-136
  122. Knopman, DS, Roberts, RO (2011) Estimating the number of persons with frontotemporal lobar degeneration in the US population. J Mol Neurosci 45: pp. 330-335
  123. Kwiatkowski, TJ, Bosco, DA, Leclerc, AL, Tamrazian, E, Vanderburg, CR, Russ, C, Davis, A, Gilchrist, J, Kasarskis, EJ, Munsat, T (2009) Mutations in the FUS/TLS gene on chromosome 16 cause familial amyotrophic lateral sclerosis. Science 323: pp. 1205-1208
  124. Kwon, I, Xiang, S, Kato, M, Wu, L, Theodoropoulos, P, Wang, T, Kim, J, Yun, J, Xie, Y, McKnight, SL (2014) Poly-dipeptides encoded by the C9orf72 repeats bind nucleoli, impede RNA biogenesis, and kill cells. Science 345: pp. 1139-1145
  125. Kwong, LK, Irwin, DJ, Walker, AK, Xu, Y, Riddle, DM, Trojanowski, JQ, Lee, VM (2014) Novel monoclonal antibodies to normal and pathologically altered human TDP-43 proteins. Acta Neuropathol Commun 2: pp. 33
  126. Lashley, T, Rohrer, JD, Bandopadhyay, R, Fry, C, Ahmed, Z, Isaacs, AM, Brelstaff, JH, Borroni, B, Warren, JD, Troakes, C (2011) A comparative clinical, pathological, biochemical and genetic study of fused in sarcoma proteinopathies. Brain 134: pp. 2548-2564
  127. Ber, I, Camuzat, A, Guillot-Noel, L, Hannequin, D, Lacomblez, L, Golfier, V, Puel, M, Martinaud, O, Deramecourt, V, Rivaud-Pechoux, S (2013) C9ORF72 repeat expansions in the frontotemporal dementias spectrum of diseases: a flow-chart for genetic testing. J Alzheimer鈥檚 Dis 34: pp. 485-499
  128. Ber, I, Camuzat, A, Hannequin, D, Pasquier, F, Guedj, E, Rovelet-Lecrux, A, Hahn-Barma, V, Zee, J, Clot, F, Bakchine, S (2008) Phenotype variability in progranulin mutation carriers: a clinical, neuropsychological, imaging and genetic study. Brain 131: pp. 732-746
  129. Ledesma, MD, Perez, M, Colaco, C, Avila, J (1998) Tau glycation is involved in aggregation of the protein but not in the formation of filaments. Cell Mol Biol 44: pp. 1111-1116
  130. Lee, EB, Lee, VM, Trojanowski, JQ (2012) Gains or losses: molecular mechanisms of TDP43-mediated neurodegeneration. Nat Rev Neurosci 13: pp. 38-50
  131. Lee, EB, Russ, J, Jung, H, Elman, LB, Chahine, LM, Kremens, D, Miller, BL, Branch Coslett, H, Trojanowski, JQ, Deerlin, VM (2013) Topography of FUS pathology distinguishes late-onset BIBD from aFTLD-U. Acta Neuropathol Commun 1: pp. 1-11
  132. Lee, SE, Khazenzon, AM, Trujillo, AJ, Guo, CC, Yokoyama, JS, Sha, SJ, Takada, LT, Karydas, AM, Block, NR, Coppola, G (2014) Altered network connectivity in frontotemporal dementia with C9orf72 hexanucleotide repeat expansion. Brain 137: pp. 3047-3060
  133. Lee, SE, Rabinovici, GD, Mayo, MC, Wilson, SM, Seeley, WW, DeArmond, SJ, Huang, EJ, Trojanowski, JQ, Growdon, ME, Jang, JY (2011) Clinicopathological correlations in corticobasal degeneration. Ann Neurol 70: pp. 327-340
  134. Lee V, Brunden K, Hutton M, Trojanoswki JQ (2012) Developing therapeutic approaches to tau, selected kinases, and related neuronal protein targets. In: Selkoe D, Holtzman DM, Mandelkow E (eds) The biology of Alzheimer disease, 1st edn. Cold Spring Harbor Laboratory Press, New York, pp 416鈥?38
  135. Litvan, I, Agid, Y, Calne, D, Campbell, G, Dubois, B, Duvoisin, RC, Goetz, CG, Golbe, LI, Grafman, J, Growdon, JH (1996) Clinical research criteria for the diagnosis of progressive supranuclear palsy (Steele鈥揜ichardson鈥揙lszewski syndrome): report of the NINDS-SPSP international workshop. Neurology 47: pp. 1-9
  136. Liu, EY, Russ, J, Wu, K, Neal, D, Suh, E, McNally, AG, Irwin, DJ, Deerlin, VM, Lee, EB (2014) C9orf72 hypermethylation protects against repeat expansion-associated pathology in ALS/FTD. Acta Neuropathol 128: pp. 525-541
  137. Luk, C, Compta, Y, Magdalinou, N, Marti, MJ, Hondhamuni, G, Zetterberg, H, Blennow, K, Constantinescu, R, Pijnenburg, Y, Mollenhauer, B (2012) Development and assessment of sensitive immuno-PCR assays for the quantification of cerebrospinal fluid three- and four-repeat tau isoforms in tauopathies. J Neurochem 123: pp. 396-405
  138. Mackenzie, IR, Arzberger, T, Kremmer, E, Troost, D, Lorenzl, S, Mori, K, Weng, SM, Haass, C, Kretzschmar, HA, Edbauer, D (2013) Dipeptide repeat protein pathology in C9ORF72 mutation cases: clinico-pathological correlations. Acta Neuropathol 126: pp. 859-879
  139. Mackenzie, IR, Neumann, M, Baborie, A, Sampathu, DM, Plessis, D, Jaros, E, Perry, RH, Trojanowski, JQ, Mann, DM, Lee, VM (2011) A harmonized classification system for FTLD-TDP pathology. Acta Neuropathol 122: pp. 111-113
  140. Mackenzie, IR, Neumann, M, Bigio, EH, Cairns, NJ, Alafuzoff, I, Kril, J, Kovacs, GG, Ghetti, B, Halliday, G, Holm, IE (2010) Nomenclature and nosology for neuropathologic subtypes of frontotemporal lobar degeneration: an update. Acta Neuropathol 119: pp. 1-4
  141. Mahoney, CJ, Beck, J, Rohrer, JD, Lashley, T, Mok, K, Shakespeare, T, Yeatman, T, Warrington, EK, Schott, JM, Fox, NC (2012) Frontotemporal dementia with the C9ORF72 hexanucleotide repeat expansion: clinical, neuroanatomical and neuropathological features. Brain 135: pp. 736-750
  142. Majounie, E, Abramzon, Y, Renton, AE, Perry, R, Bassett, SS, Pletnikova, O, Troncoso, JC, Hardy, J, Singleton, AB, Traynor, BJ (2012) Repeat expansion in C9ORF72 in Alzheimer鈥檚 disease. N Engl J Med 366: pp. 283-284
  143. Majounie, E, Renton, AE, Mok, K, Dopper, EG, Waite, A, Rollinson, S, Chio, A, Restagno, G, Nicolaou, N, Simon-Sanchez, J (2012) Frequency of the C9orf72 hexanucleotide repeat expansion in patients with amyotrophic lateral sclerosis and frontotemporal dementia: a cross-sectional study. Lancet Neurol 11: pp. 323-330
  144. Mann, DM, Rollinson, S, Robinson, A, Bennion Callister, J, Thompson, JC, Snowden, JS, Gendron, T, Petrucelli, L, Masuda-Suzukake, M, Hasegawa, M (2013) 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. Acta Neuropathol Commun 1: pp. 68
  145. Martinez-Lage, M, Molina-Porcel, L, Falcone, D, McCluskey, L, Lee, VM, Deerlin, VM, Trojanowski, JQ (2012) TDP-43 pathology in a case of hereditary spastic paraplegia with a NIPA1/SPG6 mutation. Acta Neuropathol 124: pp. 285-291
  146. Maruyama, M, Shimada, H, Suhara, T, Shinotoh, H, Ji, B, Maeda, J, Zhang, MR, Trojanowski, JQ, Lee, VM, Ono, M (2013) Imaging of tau pathology in a tauopathy mouse model and in Alzheimer patients compared to normal controls. Neuron 79: pp. 1094-1108
  147. Mattsson, N, Andreasson, U, Persson, S, Arai, H, Batish, SD, Bernardini, S, Bocchio-Chiavetto, L, Blankenstein, MA, Carrillo, MC, Chalbot, S (2011) The Alzheimer鈥檚 Association external quality control program for cerebrospinal fluid biomarkers. Alzheimer鈥檚 Dement J Alzheimer鈥檚 Assoc 7: pp. e386
  148. McCluskey, L, Vandriel, S, Elman, L, Deerlin, VM, Powers, J, Boller, A, Wood, EM, Woo, J, McMillan, CT, Rascovsky, K (2014) ALS-Plus syndrome: non-pyramidal features in a large ALS cohort. J Neurol Sci 345: pp. 118-124
  149. McMillan C, Irwin D, Avants B, Powers J, Cook PA, McCarty Wood E, Van Deerlin V, Lee V, Trojanoswki JQ, Grossman M (2013) White matter imaging helps dissociate tau from TDP-43 in frontotemporal lobar degeneration. J Neurol Neurosurg Psychiatry (under review)
  150. McMillan CT, Avants B, Irwin DJ, Toledo JB, Wolk DA, Van Deerlin VM, Shaw LM, Trojanoswki JQ, Grossman M (2012) Can MRI screen for CSF biomarkers in neurodegenerative disease? Neurology. doi:10.1212/WNL.0b013e31827b9147
  151. McMillan, CT, Avants, BB, Cook, P, Ungar, L, Trojanowski, JQ, Grossman, M (2014) The power of neuroimaging biomarkers for screening frontotemporal dementia. Hum Brain Mapp 35: pp. 4827-4840
  152. McMillan, CT, Brun, C, Siddiqui, S, Churgin, M, Libon, D, Yushkevich, P, Zhang, H, Boller, A, Gee, J, Grossman, M (2012) White matter imaging contributes to the multimodal diagnosis of frontotemporal lobar degeneration. Neurology 78: pp. 1761-1768
  153. McMillan, CT, Toledo, JB, Avants, BB, Cook, PA, Wood, EM, Suh, E, Irwin, DJ, Powers, J, Olm, C, Elman, L (2014) Genetic and neuroanatomic associations in sporadic frontotemporal lobar degeneration. Neurobiol Aging 35: pp. 1473-1482
  154. Mesulam, MM, Weintraub, S, Rogalski, EJ, Wieneke, C, Geula, C, Bigio, EH (2014) Asymmetry and heterogeneity of Alzheimer鈥檚 and frontotemporal pathology in primary progressive aphasia. Brain 137: pp. 1176-1192
  155. Meyer, H, Bug, M, Bremer, S (2012) Emerging functions of the VCP/p97 AAA-ATPase in the ubiquitin system. Nat Cell Biol 14: pp. 117-123
  156. Min, SW, Cho, SH, Zhou, Y, Schroeder, S, Haroutunian, V, Seeley, WW, Huang, EJ, Shen, Y, Masliah, E, Mukherjee, C (2010) Acetylation of tau inhibits its degradation and contributes to tauopathy. Neuron 67: pp. 953-966
  157. Mizielinska, S, Gronke, S, Niccoli, T, Ridler, CE, Clayton, EL, Devoy, A, Moens, T, Norona, FE, Woollacott, IO, Pietrzyk, J (2014) C9orf72 repeat expansions cause neurodegeneration in Drosophila through arginine-rich proteins. Science 345: pp. 1192-1194
  158. Mizielinska, S, Lashley, T, Norona, FE, Clayton, EL, Ridler, CE, Fratta, P, Isaacs, AM (2013) C9orf72 frontotemporal lobar degeneration is characterised by frequent neuronal sense and antisense RNA foci. Acta Neuropathol 126: pp. 845-857
  159. Montine, TJ, Phelps, CH, Beach, TG, Bigio, EH, Cairns, NJ, Dickson, DW, Duyckaerts, C, Frosch, MP, Masliah, E, Mirra, SS (2012) National Institute on Aging-Alzheimer鈥檚 Association guidelines for the neuropathologic assessment of Alzheimer鈥檚 disease: a practical approach. Acta Neuropathol 123: pp. 1-11
  160. Montpetit, V, Clapin, DF, Guberman, A (1985) Substructure of 20聽nm filaments of progressive supranuclear palsy. Acta Neuropathol 68: pp. 311-318
  161. Mori, K, Weng, SM, Arzberger, T, May, S, Rentzsch, K, Kremmer, E, Schmid, B, Kretzschmar, HA, Cruts, M, Broeckhoven, C (2013) The C9orf72 GGGGCC repeat is translated into aggregating dipeptide-repeat proteins in FTLD/ALS. Science 339: pp. 1335-1338
  162. Morris, HR, Baker, M, Yasojima, K, Houlden, H, Khan, MN, Wood, NW (2002) Analysis of tau haplotypes in Pick鈥檚 disease. Neurology 59: pp. 443-445
  163. Mukherjee, O, Pastor, P, Cairns, NJ, Chakraverty, S, Kauwe, JS, Shears, S, Behrens, MI, Budde, J, Hinrichs, AL, Norton, J (2006) HDDD2 is a familial frontotemporal lobar degeneration with ubiquitin-positive, tau-negative inclusions caused by a missense mutation in the signal peptide of progranulin. Ann Neurol 60: pp. 314-322
  164. Munoz-Garcia, D, Ludwin, SK (1984) Classic and generalized variants of Pick鈥檚 disease: a clinicopathological, ultrastructural, and immunocytochemical comparative study. Ann Neurol 16: pp. 467-480
  165. Munoz, DG, Neumann, M, Kusaka, H, Yokota, O, Ishihara, K, Terada, S, Kuroda, S, Mackenzie, IR (2009) FUS pathology in basophilic inclusion body disease. Acta Neuropathol 118: pp. 617-627
  166. Murray, R, Neumann, M, Forman, MS, Farmer, J, Massimo, L, Rice, A, Miller, BL, Johnson, JK, Clark, CM, Hurtig, HI (2007) Cognitive and motor assessment in autopsy-proven corticobasal degeneration. Neurology 68: pp. 1274-1283
  167. Nakashima-Yasuda, H, Uryu, K, Robinson, J, Xie, SX, Hurtig, H, Duda, JE, Arnold, SE, Siderowf, A, Grossman, M, Leverenz, JB (2007) Co-morbidity of TDP-43 proteinopathy in Lewy body related diseases. Acta Neuropathol 114: pp. 221-229
  168. Nelson, PT, Schmitt, FA, Lin, Y, Abner, EL, Jicha, GA, Patel, E, Thomason, PC, Neltner, JH, Smith, CD, Santacruz, KS (2011) Hippocampal sclerosis in advanced age: clinical and pathological features. Brain 134: pp. 1506-1518
  169. Neumann, M (2013) Frontotemporal lobar degeneration and amyotrophic lateral sclerosis: molecular similarities and differences. Revue Neurol 169: pp. 793-798
  170. Neumann, M, Bentmann, E, Dormann, D, Jawaid, A, DeJesus-Hernandez, M, Ansorge, O, Roeber, S, Kretzschmar, HA, Munoz, DG, Kusaka, H (2011) FET proteins TAF15 and EWS are selective markers that distinguish FTLD with FUS pathology from amyotrophic lateral sclerosis with FUS mutations. Brain 134: pp. 2595-2609
  171. Neumann, M, Kwong, LK, Lee, EB, Kremmer, E, Flatley, A, Xu, Y, Forman, MS, Troost, D, Kretzschmar, HA, Trojanowski, JQ (2009) Phosphorylation of S409/410 of TDP-43 is a consistent feature in all sporadic and familial forms of TDP-43 proteinopathies. Acta Neuropathol 117: pp. 137-149
  172. Neumann, M, Roeber, S, Kretzschmar, HA, Rademakers, R, Baker, M, Mackenzie, IR (2009) Abundant FUS-immunoreactive pathology in neuronal intermediate filament inclusion disease. Acta Neuropathol 118: pp. 605-616
  173. Neumann, M, Sampathu, DM, Kwong, LK, Truax, AC, Micsenyi, MC, Chou, TT, Bruce, J, Schuck, T, Grossman, M, Clark, CM (2006) Ubiquitinated TDP-43 in frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Science 314: pp. 130-133
  174. Nonaka, T, Masuda-Suzukake, M, Arai, T, Hasegawa, Y, Akatsu, H, Obi, T, Yoshida, M, Murayama, S, Mann, DM, Akiyama, H (2013) Prion-like properties of pathological TDP-43 aggregates from diseased brains. Cell Rep 4: pp. 124-134
  175. Onyike, CU, Diehl-Schmid, J (2013) The epidemiology of frontotemporal dementia. Int Rev Psychiatry 25: pp. 130-137
  176. Ou, SH, Wu, F, Harrich, D, Garcia-Martinez, LF, Gaynor, RB (1995) Cloning and characterization of a novel cellular protein, TDP-43, that binds to human immunodeficiency virus type 1 TAR DNA sequence motifs. J Virol 69: pp. 3584-3596
  177. Proudfoot, M, Gutowski, NJ, Edbauer, D, Hilton, DA, Stephens, M, Rankin, J, Mackenzie, IR (2014) Early dipeptide repeat pathology in a frontotemporal dementia kindred with C9ORF72 mutation and intellectual disability. Acta Neuropathol 127: pp. 451-458
  178. Rabinovici, GD, Jagust, WJ, Furst, AJ, Ogar, JM, Racine, CA, Mormino, EC, O鈥橬eil, JP, Lal, RA, Dronkers, NF, Miller, BL (2008) Abeta amyloid and glucose metabolism in three variants of primary progressive aphasia. Ann Neurol 64: pp. 388-401
  179. Rascovsky, K, Hodges, JR, Knopman, D, Mendez, MF, Kramer, JH, Neuhaus, J, Swieten, JC, Seelaar, H, Dopper, EG, Onyike, CU (2011) Sensitivity of revised diagnostic criteria for the behavioural variant of frontotemporal dementia. Brain 134: pp. 2456-2477
  180. Ratnavalli, E, Brayne, C, Dawson, K, Hodges, JR (2002) The prevalence of frontotemporal dementia. Neurology 58: pp. 1615-1621
  181. Renton, AE, Majounie, E, Waite, A, Simon-Sanchez, J, Rollinson, S, Gibbs, JR, Schymick, JC, Laaksovirta, H, Swieten, JC, Myllykangas, L (2011) A hexanucleotide repeat expansion in C9ORF72 is the cause of chromosome 9p21-linked ALS-FTD. Neuron 72: pp. 257-268
  182. Robinson, JL, Geser, F, Stieber, A, Umoh, M, Kwong, LK, Deerlin, VM, Lee, VM, Trojanowski, JQ (2013) TDP-43 skeins show properties of amyloid in a subset of ALS cases. Acta Neuropathol 125: pp. 121-131
  183. Rohrer, JD, Lashley, T, Schott, JM, Warren, JE, Mead, S, Isaacs, AM, Beck, J, Hardy, J, Silva, R, Warrington, E (2011) Clinical and neuroanatomical signatures of tissue pathology in frontotemporal lobar degeneration. Brain 134: pp. 2565-2581
  184. Rollinson, S, Mead, S, Snowden, J, Richardson, A, Rohrer, J, Halliwell, N, Usher, S, Neary, D, Mann, D, Hardy, J (2011) Frontotemporal lobar degeneration genome wide association study replication confirms a risk locus shared with amyotrophic lateral sclerosis. Neurobiol Aging 32: pp. e751-e757
  185. Rosso, SM, Landweer, EJ, Houterman, M, Donker Kaat, L, Duijn, CM, Swieten, JC (2003) Medical and environmental risk factors for sporadic frontotemporal dementia: a retrospective case-control study. J Neurol Neurosurg Psychiatry 74: pp. 1574-1576
  186. Russ J, Liu EY, Wu K, Neal D, Suh E, Irwin DJ, McMillan CT, Harms MB, Cairns NJ, Wood EMet al (2014) Hypermethylation of repeat expanded C9orf72 is a clinical and molecular disease modifier. Acta Neuropathol. doi:10.1007/s00401-014-1365-0
  187. Saito, Y, Ruberu, NN, Sawabe, M, Arai, T, Tanaka, N, Kakuta, Y, Yamanouchi, H, Murayama, S (2004) Staging of argyrophilic grains: an age-associated tauopathy. J Neuropathol Exp Neurol 63: pp. 911-918
  188. Sampathu, DM, Neumann, M, Kwong, LK, Chou, TT, Micsenyi, M, Truax, A, Bruce, J, Grossman, M, Trojanowski, JQ, Lee, VM (2006) Pathological heterogeneity of frontotemporal lobar degeneration with ubiquitin-positive inclusions delineated by ubiquitin immunohistochemistry and novel monoclonal antibodies. Am J Pathol 169: pp. 1343-1352
  189. Santa-Maria, I, Haggiagi, A, Liu, X, Wasserscheid, J, Nelson, PT, Dewar, K, Clark, LN, Crary, JF (2012) The MAPT H1 haplotype is associated with tangle-predominant dementia. Acta Neuropathol 124: pp. 693-704
  190. Scherling, CS, Hall, T, Berisha, F, Klepac, K, Karydas, A, Coppola, G, Kramer, JH, Rabinovici, G, Ahlijanian, M, Miller, BL (2014) Cerebrospinal fluid neurofilament concentration reflects disease severity in frontotemporal degeneration. Ann Neurol 75: pp. 116-126
  191. Sha, SJ, Takada, LT, Rankin, KP, Yokoyama, JS, Rutherford, NJ, Fong, JC, Khan, B, Karydas, A, Baker, MC, DeJesus-Hernandez, M (2012) Frontotemporal dementia due to C9ORF72 mutations: clinical and imaging features. Neurology 79: pp. 1002-1011
  192. Shaw, LM, Vanderstichele, H, Knapik-Czajka, M, Clark, CM, Aisen, PS, Petersen, RC, Blennow, K, Soares, H, Simon, A, Lewczuk, P (2009) Cerebrospinal fluid biomarker signature in Alzheimer鈥檚 disease neuroimaging initiative subjects. Ann Neurol 65: pp. 403-413
  193. Shaw, LM, Vanderstichele, H, Knapik-Czajka, M, Figurski, M, Coart, E, Blennow, K, Soares, H, Simon, AJ, Lewczuk, P, Dean, RA (2011) Qualification of the analytical and clinical performance of CSF biomarker analyses in ADNI. Acta Neuropathol 121: pp. 597-609
  194. Simon-Sanchez, J, Dopper, EG, Cohn-Hokke, PE, Hukema, RK, Nicolaou, N, Seelaar, H, Graaf, JR, Koning, I, Schoor, NM, Deeg, DJ (2012) The clinical and pathological phenotype of C9ORF72 hexanucleotide repeat expansions. Brain 135: pp. 723-735
  195. Skillback, T, Farahmand, B, Bartlett, JW, Rosen, C, Mattsson, N, Nagga, K, Kilander, L, Religa, D, Wimo, A, Winblad, B (2014) CSF neurofilament light differs in neurodegenerative diseases and predicts severity and survival. Neurology 83: pp. 1945-1953
  196. Sleegers, K, Brouwers, N, Damme, P, Engelborghs, S, Gijselinck, I, Zee, J, Peeters, K, Mattheijssens, M, Cruts, M, Vandenberghe, R (2009) Serum biomarker for progranulin-associated frontotemporal lobar degeneration. Ann Neurol 65: pp. 603-609
  197. Snowden, J, Neary, D, Mann, D (2007) Frontotemporal lobar degeneration: clinical and pathological relationships. Acta Neuropathol 114: pp. 31-38
  198. Snowden, JS, Hu, Q, Rollinson, S, Halliwell, N, Robinson, A, Davidson, YS, Momeni, P, Baborie, A, Griffiths, TD, Jaros, E (2011) The most common type of FTLD-FUS (aFTLD-U) is associated with a distinct clinical form of frontotemporal dementia but is not related to mutations in the FUS gene. Acta Neuropathol 122: pp. 99-110
  199. Snowden, JS, Rollinson, S, Thompson, JC, Harris, JM, Stopford, CL, Richardson, AM, Jones, M, Gerhard, A, Davidson, YS, Robinson, A (2012) Distinct clinical and pathological characteristics of frontotemporal dementia associated with C9ORF72 mutations. Brain 135: pp. 693-708
  200. Steinacker, P, Hendrich, C, Sperfeld, AD, Jesse, S, Arnim, CA, Lehnert, S, Pabst, A, Uttner, I, Tumani, H, Lee, VM (2008) TDP-43 in cerebrospinal fluid of patients with frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Arch Neurol 65: pp. 1481-1487
  201. Strong, MJ, Grace, GM, Freedman, M, Lomen-Hoerth, C, Woolley, S, Goldstein, LH, Murphy, J, Shoesmith, C, Rosenfeld, J, Leigh, PN (2009) Consensus criteria for the diagnosis of frontotemporal cognitive and behavioural syndromes in amyotrophic lateral sclerosis. Amyotroph Lateral Scler 10: pp. 131-146
  202. Su, Z, Zhang, Y, Gendron, TF, Bauer, PO, Chew, J, Yang, WY, Fostvedt, E, Jansen-West, K, Belzil, VV, Desaro, P (2014) Discovery of a biomarker and lead small molecules to target r(GGGGCC)-associated defects in c9FTD/ALS. Neuron 83: pp. 1043-1050
  203. Toledo, JB, Brettschneider, J, Grossman, M, Arnold, SE, Hu, WT, Xie, SX, Lee, VM, Shaw, LM, Trojanowski, JQ (2012) CSF biomarkers cutoffs: the importance of coincident neuropathological diseases. Acta Neuropathol 124: pp. 23-35
  204. Urwin, H, Josephs, KA, Rohrer, JD, Mackenzie, IR, Neumann, M, Authier, A, Seelaar, H, Swieten, JC, Brown, JM, Johannsen, P (2010) FUS pathology defines the majority of tau- and TDP-43-negative frontotemporal lobar degeneration. Acta Neuropathol 120: pp. 33-41
  205. Uryu, K, Nakashima-Yasuda, H, Forman, MS, Kwong, LK, Clark, CM, Grossman, M, Miller, BL, Kretzschmar, HA, Lee, VM, Trojanowski, JQ (2008) Concomitant TAR-DNA-binding protein 43 pathology is present in Alzheimer disease and corticobasal degeneration but not in other tauopathies. J Neuropathol Exp Neurol 67: pp. 555-564
  206. Blitterswijk, M, Mullen, B, Wojtas, A, Heckman, MG, Diehl, NN, Baker, MC, DeJesus-Hernandez, M, Brown, PH, Murray, ME, Hsiung, GY (2014) Genetic modifiers in carriers of repeat expansions in the C9ORF72 gene. Mol Neurodegener 9: pp. 38
  207. Deerlin, VM, Leverenz, JB, Bekris, LM, Bird, TD, Yuan, W, Elman, LB, Clay, D, Wood, EM, Chen-Plotkin, AS, Martinez-Lage, M (2008) TARDBP mutations in amyotrophic lateral sclerosis with TDP-43 neuropathology: a genetic and histopathological analysis. Lancet Neurol 7: pp. 409-416
  208. Deerlin, VM, Sleiman, PM, Martinez-Lage, M, Chen-Plotkin, A, Wang, LS, Graff-Radford, NR, Dickson, DW, Rademakers, R, Boeve, BF, Grossman, M (2010) Common variants at 7p21 are associated with frontotemporal lobar degeneration with TDP-43 inclusions. Nat Genet 42: pp. 234-239
  209. Zee, J, Langenhove, T, Kleinberger, G, Sleegers, K, Engelborghs, S, Vandenberghe, R, Santens, P, Broeck, M, Joris, G, Brys, J (2011) TMEM106B is associated with frontotemporal lobar degeneration in a clinically diagnosed patient cohort. Brain 134: pp. 808-815
  210. Vance, C, Rogelj, B, Hortobagyi, T, Vos, KJ, Nishimura, AL, Sreedharan, J, Hu, X, Smith, B, Ruddy, D, Wright, P (2009) Mutations in FUS, an RNA processing protein, cause familial amyotrophic lateral sclerosis type 6. Science 323: pp. 1208-1211
  211. Vanderstichele, H, Bibl, M, Engelborghs, S, Bastard, N, Lewczuk, P, Molinuevo, JL, Parnetti, L, Perret-Liaudet, A, Shaw, LM, Teunissen, C (2012) Standardization of preanalytical aspects of cerebrospinal fluid biomarker testing for Alzheimer鈥檚 disease diagnosis: a consensus paper from the Alzheimer鈥檚 Biomarkers Standardization Initiative. Alzheimer鈥檚 Dement J Alzheimer鈥檚 Assoc 8: pp. 65-73
  212. Villela, D, Kimura, L, Schlesinger, D, Goncalves, A, Pearson, PL, Suemoto, CK, Pasqualucci, C, Krepischi, AC, Grinberg, LT, Rosenberg, C (2013) Germline DNA copy number variation in individuals with Argyrophilic grain disease reveals CTNS as a plausible candidate gene. Genet Mol Biol 36: pp. 498-501
  213. Wakabayashi, K, Oyanagi, K, Makifuchi, T, Ikuta, F, Homma, A, Homma, Y, Horikawa, Y, Tokiguchi, S (1994) Corticobasal degeneration: etiopathological significance of the cytoskeletal alterations. Acta Neuropathol 87: pp. 545-553
  214. Watts, GD, Thomasova, D, Ramdeen, SK, Fulchiero, EC, Mehta, SG, Drachman, DA, Weihl, CC, Jamrozik, Z, Kwiecinski, H, Kaminska, A (2007) Novel VCP mutations in inclusion body myopathy associated with Paget disease of bone and frontotemporal dementia. Clin Genet 72: pp. 420-426
  215. Watts, GD, Wymer, J, Kovach, MJ, Mehta, SG, Mumm, S, Darvish, D, Pestronk, A, Whyte, MP, Kimonis, VE (2004) Inclusion body myopathy associated with Paget disease of bone and frontotemporal dementia is caused by mutant valosin-containing protein. Nat Genet 36: pp. 377-381
  216. Whitwell, JL, Josephs, KA (2011) Neuroimaging in frontotemporal lobar degeneration鈥攑redicting molecular pathology. Nat Rev Neurol 8: pp. 131-142
  217. Wilson, RS, Yu, L, Trojanowski, JQ, Chen, EY, Boyle, PA, Bennett, DA, Schneider, JA (2013) TDP-43 pathology, cognitive decline, and dementia in old age. JAMA Neurol 70: pp. 1418-1424
  218. Wood EM, Falcone D, Suh E, Irwin DJ, Chen-Plotkin AS, Lee EB, Xie SX, Van Deerlin VM, Grossman M (2013) Development and validation of pedigree classification criteria for frontotemporal lobar degeneration. JAMA Neurol. doi:10.1001/jamaneurol.2013.3956
  219. Yoshiyama, Y, Lee, VM, Trojanowski, JQ (2013) Therapeutic strategies for tau mediated neurodegeneration. J Neurol Neurosurg Psychiatry 84: pp. 784-795
  220. Zhang, YJ, Jansen-West, K, Xu, YF, Gendron, TF, Bieniek, KF, Lin, WL, Sasaguri, H, Caulfield, T, Hubbard, J, Daughrity, L (2014) Aggregation-prone c9FTD/ALS poly(GA) RAN-translated proteins cause neurotoxicity by inducing ER stress. Acta Neuropathol 128: pp. 505-524
  221. Zhukareva, V, Joyce, S, Schuck, T, Deerlin, V, Hurtig, H, Albin, R, Gilman, S, Chin, S, Miller, B, Trojanowski, JQ (2006) Unexpected abundance of pathological tau in progressive supranuclear palsy white matter. Ann Neurol 60: pp. 335-345
  222. Zhukareva, V, Mann, D, Pickering-Brown, S, Uryu, K, Shuck, T, Shah, K, Grossman, M, Miller, BL, Hulette, CM, Feinstein, SC (2002) Sporadic Pick鈥檚 disease: a tauopathy characterized by a spectrum of pathological tau isoforms in gray and white matter. Ann Neurol 51: pp. 730-739
  223. Zhukareva, V, Shah, K, Uryu, K, Braak, H, Tredici, K, Sundarraj, S, Clark, C, Trojanowski, JQ, Lee, VM (2002) Biochemical analysis of tau proteins in argyrophilic grain disease, Alzheimer鈥檚 disease, and Pick鈥檚 disease: a comparative study. Am J Pathol 161: pp. 1135-1141
  224. Zhukareva, V, Trojanowski, JQ, Lee, VM (2004) Assessment of pathological tau proteins in frontotemporal dementias: qualitative and quantitative approaches. Am J Geriatr Psychiatry 12: pp. 136-145
  
• 刊物类别：Medicine
• 刊物主题：Medicine & Public Health
  Pathology
  
• 出版者：Springer Berlin / Heidelberg
• ISSN：1432-0533

文摘

Frontotemporal lobar degeneration (FTLD) comprises two main classes of neurodegenerative diseases characterized by neuronal/glial proteinaceous inclusions (i.e., proteinopathies) including tauopathies (i.e., FTLD-Tau) and TDP-43 proteinopathies (i.e., FTLD-TDP) while other very rare forms of FTLD are known such as FTLD with FUS pathology (FTLD-FUS). This review focuses mainly on FTLD-Tau and FLTD-TDP, which may present as several clinical syndromes: a behavioral/dysexecutive syndrome (behavioral variant frontotemporal dementia); language disorders (primary progressive aphasia variants); and motor disorders (amyotrophic lateral sclerosis, corticobasal syndrome, progressive supranuclear palsy syndrome). There is considerable heterogeneity in clinical presentations of underlying neuropathology and current clinical criteria do not reliably predict underlying proteinopathies ante-mortem. In contrast, molecular etiologies of hereditary FTLD are consistently associated with specific proteinopathies. These include MAPT mutations with FTLD-Tau and GRN, C9orf72, VCP and TARDBP with FTLD-TDP. The last decade has seen a rapid expansion in our knowledge of the molecular pathologies associated with this clinically and neuropathologically heterogeneous group of FTLD diseases. Moreover, in view of current limitations to reliably diagnose specific FTLD neuropathologies prior to autopsy, we summarize the current state of the science in FTLD biomarker research including neuroimaging, biofluid and genetic analyses. We propose that combining several of these biomarker modalities will improve diagnostic specificity in FTLD through a personalized medicine approach. The goals of these efforts are to enhance power for clinical trials focused on slowing or preventing progression of spread of tau, TDP-43 and other FTLD-associated pathologies and work toward the goal of defining clinical endophenotypes of FTD.