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Frontotemporal Lobar Degeneration

  • Enrico Premi
  • Alessandro Padovani
  • Barbara Borroni
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 724)

Abstract

Frontotemporal Lobar Degeneration (FTLD) is an heterogeneous neurodegenerative disorder characterized by behaviour and language disturbances, associated with degeneration of the frontal and temporal lobes. Three different clinical presentations have been described, namely behavioural variant Frontotemporal Dementia (bvFTD), Semantic Dementia (SD) and Progressive Non-Fluent Aphasia (PNFA). The associated histopathology includes different neuropathological hallmarks, the most frequent being tau-positive inclusions (FTLD-TAU) or tau-negative and TDP-43 positive inclusions (FTLD-TDP). The majority of familial FTLD cases are caused by mutations within Microtubule-Associated Protein Tau (MAPT) gene, leading to FTLD-TAU, or Progranulin (PGRN) gene, leading to FTLD-TDP. In the last few years, imaging, biological and genetic biomarkers have been developed, helping in clinical evaluation and diagnostic accuracy. Though current pharmacologic interventions are only symptomatic, recent research argues for possible disease-modifying strategies in the near future.

Keywords

Amyotrophic Lateral Sclerosis Neurodegenerative Disease Neurol Neurosurg Psychiatry Motor Neuron Disease Semantic Dementia 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. 1.
    Pick A. Uber die Beziehungen der senilen Hirnatrophie zur Aphasie. Prager Med Wochenschr 1882; 17:165–167.Google Scholar
  2. 2.
    Kertesz A, McMonagle P, Blair M et al. The evolution and pathology of frontotemporal dementia. Brain 2005; 128:1996–2005.PubMedCrossRefGoogle Scholar
  3. 3.
    Gans A. Betrachtungen uber Art und Ausbreitung des Krankhaften Prozessess in einem Fall von Pickscher Atrophie des Sternhirns. Z Gesamte Neurol Psychiatr 1922; 80:10–28.CrossRefGoogle Scholar
  4. 4.
    Onari K, Spatz H. Anatomische Beitaege zur lehre von Pickschen umschriebenen Grosshirnrinden-Atrophie (“Picksche Krankheit”). Z Gesamte Neurol Psychiatr 1926; 101:470–511.CrossRefGoogle Scholar
  5. 5.
    Schneider C. Uber Picksche Krankheit. Monatschr Psychiatr Neurol 1927; 65:230–275.CrossRefGoogle Scholar
  6. 6.
    Neary D, Snowden JS, Goulding P et al. Dementia of frontal lobe type. J Neurol Neurosurg Psychiatry 1988; 51:353–361.PubMedCrossRefGoogle Scholar
  7. 7.
    Gustafson L. Frontal lobe degeneration of non-Alzheimer type II. Clinical picture and differential diagnosis. Arch Gerontol Geriatr 1987; 6:209–223.PubMedCrossRefGoogle Scholar
  8. 8.
    Lund and Manchester Groups. Consensus statement. Clinical and neuropathological criteria for frontotemporal dementia. J Neurol Neurosurg Psychiatry 1994; 57:416–418.CrossRefGoogle Scholar
  9. 9.
    Miller BL, Ikonte BS, Ponton M et al. A study of the Lund-Manchester research criteria for frontotemporal dementia: clinical and single photon emission CT correlations. Neurology 1997; 48:937–942.PubMedGoogle Scholar
  10. 10.
    Neary D, Snowden JS, Gustafson L et al. Frontotemporal lobar degeneration: a consensus on clinical diagnostic criteria. Neurology 1998; 51:1546–1554.PubMedGoogle Scholar
  11. 11.
    Edwards-Lee T, Miller BL, Benson DF et al. The temporal variant of frontotemporal dementia. Brain. 1997; 120(Pt 6):1027–1040.PubMedCrossRefGoogle Scholar
  12. 12.
    McKhann GM, Dickson D, Trojanowski JQ et al. Clinical and Pathological Diagnosis of Frontotemporal Dementia. Report of the work group on frontotemporal dementia and Pick’s disease. Arch Neurol 2001; 58:1803–1809.PubMedCrossRefGoogle Scholar
  13. 13.
    Skibinski G, Parkinson NJ, Brown JM et al. Mutations in the endosomal ESCRTIII-complex subunit CHMP2B in frontotemporal dementia. Nat Genet 2005; 37(8):806–808PubMedCrossRefGoogle Scholar
  14. 14.
    Ratnavalli E, Brayne C, Dawson K et al. The prevalence of frontotemporal dementia. Neurology 2002; 58:1615–1621.PubMedGoogle Scholar
  15. 15.
    Ikeda M, Ishikawa T, Tanabe H. Epidemiology of Frontotemporal Lobar Degeneration. Dement Geriatr Cogn Disord 2004; 17:265–268.PubMedCrossRefGoogle Scholar
  16. 16.
    Rosso SM, Donker Kaat L, Baks T et al. Frontotemporal dementia in the Netherlands: patient characteristics and prevalence estimates from a population-based study. Brain 2003; 126:2016–2022.PubMedCrossRefGoogle Scholar
  17. 17.
    Mercy L, Hodges JR, Dawson K et al. Incidence of early-onset dementias in Cambridgeshire, United Kingdom. Neurology 2008; 71:1496–1499.PubMedCrossRefGoogle Scholar
  18. 18.
    Knopman DS, Petersen RC, Edland SD et al. The incidence of frontotemporal lobar degeneration in Rochester, Minnesota, 1990 through 1994. Neurology 2004; 62:506–508.PubMedGoogle Scholar
  19. 19.
    Borroni B, Alberici A, Grassi M et al. Is frontotemporal lobar degeneration a rare disorder? Evidence from a preliminary study in Brescia county, Italy. J Alzheimers Dis 2010; 19(1):111–116.PubMedGoogle Scholar
  20. 20.
    Kertesz A, Blair M, McMonagle P et al. The diagnosis and course of frontotemporal dementia. Alzheimer Dis Assoc Disord 2007; 21:155–163.PubMedCrossRefGoogle Scholar
  21. 21.
    Roberson ED, Hesse JH, Rose KD et al. Frontotemporal dementia progresses to death faster than Alzheimer disease. Neurology 2005; 65:719–725.PubMedCrossRefGoogle Scholar
  22. 22.
    Liu W, Miller BL, Kramer JH et al. Behavioral disorders in the frontal and temporal variants of frontotemporal dementia. Neurology 2004; 62:742–748.PubMedGoogle Scholar
  23. 23.
    Mendez MF, Shapira JS, Miller BL. Stereotypical movements and frontotemporal dementia. Mov Disord 2005; 20:742–745.PubMedCrossRefGoogle Scholar
  24. 24.
    Ikeda M, Brown J, Holland AJ et al. Changes in appetite, food preference and eating habits in frontotemporal dementia and Alzheimer’s disease. J Neurol Neurosurg Psychiatry 2002; 73:371–376PubMedCrossRefGoogle Scholar
  25. 25.
    Miller BL, Seeley WW, Mychack P et al. Neuroanatomy of the self: evidence from patients with frontotemporal dementia. Neurology 2001; 57:817–821.PubMedGoogle Scholar
  26. 26.
    Kramer JH, Jurik J, Sha SJ et al. Distinctive neuropsychological patterns in frontotemporal dementia, semantic dementia and Alzheimer disease. Cogn Behav Neurol 2003; 16:211–218.PubMedCrossRefGoogle Scholar
  27. 27.
    Levy ML, Miller BL, Cummings JL et al. Alzheimer disease and frontotemporal dementias: behavioral distinctions. Arch Neurol 1996; 53:687–690.PubMedCrossRefGoogle Scholar
  28. 28.
    Rosen HJ, Gorno-Tempini ML, Goldman WP et al. Patterns of brain atrophy in frontotemporal dementia and semantic dementia. Neurology 2002; 58:198–208.PubMedGoogle Scholar
  29. 29.
    McNeill R, Sare GM, Manoharan M, Testa et al. J Neurol Neurosurg Psychiatry 2007; 78(4):350–355.PubMedCrossRefGoogle Scholar
  30. 30.
    Grimmer T, Diehl J, Drzezga A et al. Region-specific decline of cerebral glucose metabolism in patients with frontotemporal dementia: a prospective 18F-FDG-PET study. Dement Geriatr Cogn Disord 2004.Google Scholar
  31. 31.
    Whitwell JL, Avula R, Senjem ML et al. Gray and white matter water diffusion in the syndromic variants of frontotemporal dementia. Neurology 2010; 74(16):1279–1287.PubMedCrossRefGoogle Scholar
  32. 32.
    Borroni B, Brambati SM, Agosti C et al. Evidence of white matter changes on diffusion tensor imaging in frontotemporal dementia. Arch Neurol 2007; 64(2):246–251.PubMedCrossRefGoogle Scholar
  33. 33.
    Rosen HJ, Allison SC, Schauer GF et al. Neuroanatomical correlates of behavioural disorders in dementia. Brain 2005; 128:2612–2625.PubMedCrossRefGoogle Scholar
  34. 34.
    Rabinovici GD, Seeley WW, Kim EJ et al. Distinct MRI atrophy patterns in autopsy-proven Alzheimer’s disease and frontotemporal lobar degeneration. Am J Alzheimers Dis Other Demen 2007; 22:474–488.PubMedCrossRefGoogle Scholar
  35. 35.
    Lomen-Hoerth C. Characterization of amyotrophic lateral sclerosis and frontotemporal dementia. Dement Geriatr Cogn Disord 2004; 17:337–341.PubMedCrossRefGoogle Scholar
  36. 36.
    Gorno-Tempini ML, Dronkers NF, Rankin KP et al. Cognition and anatomy in three variants of primary progressive aphasia. Ann Neurol 2004; 55:335–346.PubMedCrossRefGoogle Scholar
  37. 37.
    Rosen HJ, Allison SC, Ogar JM et al. Behavioral features in semantic dementia vs other forms of progressive aphasias. Neurology 2006; 67:1752–1756.PubMedCrossRefGoogle Scholar
  38. 38.
    Josephs KA, Duffy JR, Strand EA et al. Clinicopathological and imaging correlates of progressive aphasia and apraxia of speech. Brain 2006; 129:1385–1398.PubMedCrossRefGoogle Scholar
  39. 39.
    Seeley WW, Bauer AM, Miller BL et al. The natural history of temporal variant frontotemporal dementia. Neurology 2005; 64:1384–1390.PubMedCrossRefGoogle Scholar
  40. 40.
    Gorno-Tempini ML, Rankin KP, Woolley JD et al. Cognitive and behavioral profile in a case of right anterior temporal lobe neurodegeneration. Cortex 2004; 40:631–644.PubMedCrossRefGoogle Scholar
  41. 41.
    Brun A. Frontal lobe degeneration of the non-Alzheimer type: I. Neuropathology Arch Gerontol Geriatr 1987; 6:193–208.CrossRefGoogle Scholar
  42. 42.
    Short RA, Broderick DF, Patton A. Different patterns of magnetic resonance imaging atrophy for frontotemporal lobar degeneration syndromes. Arch Neurol 2005; 62(7):1106–1110.PubMedCrossRefGoogle Scholar
  43. 43.
    Dickson DW. Neuropathology of Pick’s disease. Neurology 2001; 56:S16–S20.PubMedGoogle Scholar
  44. 44.
    Mackenzie IR, Neumann M, Bigio EH. Nomenclature and nosology for neuropathologic subtypes of frontotemporal lobar degeneration: an update. Acta Neuropathol 2010; 119:1–4.PubMedCrossRefGoogle Scholar
  45. 45.
    Spillantini MG, Goedert M. Tau protein pathology in neurodegenerative diseases. Trends Neurosci 1998; 21:428–433.PubMedCrossRefGoogle Scholar
  46. 46.
    Lee G, Neve RL, Kosik KS. The microtubule binding domain of tau protein. Neuron 1989; 2:1615–1624.PubMedCrossRefGoogle Scholar
  47. 47.
    Andreadis A, Brown WM, Kosik KS. Structure and novel exons of the human tau gene. Biochemistry 1992; 31:10626–10633.PubMedCrossRefGoogle Scholar
  48. 48.
    Cooper PN, Jackson M, Lennox G et al. Tau, ubiquitin and alpha B-crystallin immunohistochemistry define the principal causes of degenerative frontotemporal dementia. Arch Neurol 1995; 52:1011–1015.PubMedCrossRefGoogle Scholar
  49. 49.
    Cairns NJ, Bigio EH, Mackenzie IR et al. Neuropathologic diagnostic and nosologic criteria for frontotemporal lobar degeneration: consensus of the Consortium for Frontotemporal Lobar Degeneration. Acta Neuropathol 2007; 114:5–22.PubMedCrossRefGoogle Scholar
  50. 50a.
    Knopman DS. Overview of dementia lacking distinctive histology: pathological designation of a progressive dementia. Dementia 1993; 4:132–136.PubMedGoogle Scholar
  51. 50b.
    Neumann M, Sampathu DM, Kwong LK et al. Ubiquitinated TDP-43 in frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Science 2006; 314:130–133.PubMedCrossRefGoogle Scholar
  52. 51.
    Neumann M, Sampathu DM, Kwong LK et al. Ubiquitinated TDP-43 in frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Science 2006; 314:130–133.PubMedCrossRefGoogle Scholar
  53. 52.
    Arai T, Hasegawa M, Akiyama H 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 2006; 351:602–611.PubMedCrossRefGoogle Scholar
  54. 53.
    Hasegawa M, Arai T, Nonaka T et al. Phosphorylated TDP-43 in frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Ann Neurol 2008; 64(1):60–70.PubMedCrossRefGoogle Scholar
  55. 54.
    Zhang YJ, Xu YF, Dickey CA et al. Progranulin mediates caspase-dependent cleavage of TAR DNA binding protein-43. J Neurosci 2007; 27:10530–10534.PubMedCrossRefGoogle Scholar
  56. 55.
    Igaz LM, Kwong LK, Xu Y et al. 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 2008; 173:182–194.PubMedCrossRefGoogle Scholar
  57. 56.
    Igaz LM, Kwong LK, Chen-Plotkin A et al. Expression of TDP-43 C-terminal fragments in vitro recapitulates pathological features of TDP-43 proteinopathies. J Biol Chem 2009; 284:8516–8524.PubMedCrossRefGoogle Scholar
  58. 57.
    Davidson Y, Kelley T, Mackenzie IR et al. Ubiquitinated pathological lesions in frontotemporal lobar degeneration contain the TAR DNA-binding protein, TDP-43. Acta Neuropathol (Berl) 2007; 113:521–533.CrossRefGoogle Scholar
  59. 58.
    Masellis M, Momeni P, Meschino W et al. Novel splicing mutation in the progranulin gene causing familial corticobasal syndrome. Brain 2006; 129:3115–3123.PubMedCrossRefGoogle Scholar
  60. 59.
    Josephs KA, Stroh A, Dugger B et al. Evaluation of subcortical pathology and clinical correlations in FTLD-U subtypes. Acta Neuropathol 2009; 118:349–358.PubMedCrossRefGoogle Scholar
  61. 60.
    Mackenzie IR, Shi J, Shaw CL et al. Dementia lacking distinctive histology (DLDH) revisited. Acta Neuropathol 2006; 112:551–559.PubMedCrossRefGoogle Scholar
  62. 61.
    Forman MS, Mackenzie IR, Cairns NJ et al. Novel ubiquitin neuropathology in frontotemporal dementia with valosin-containing protein gene mutations. J Neuropathol Exp Neurol 2006; 65:571–581.PubMedCrossRefGoogle Scholar
  63. 62.
    Sreedharan J, Blair IP, Tripathi VB et al. TDP-43 mutations in familial and sporadic amyotrophic lateral sclerosis. Science 2008; 319:1668–1672.PubMedCrossRefGoogle Scholar
  64. 63.
    Buratti E, Baralle FE. Multiple roles of TDP-43 in gene expression, splicing regulation and human disease. Front Biosci 2008; 13:867–878.PubMedCrossRefGoogle Scholar
  65. 64.
    Kabashi E, Lin L, Tradewell ML et al. Gain and loss of function of ALS-related mutations of TARDBP (TDP-43) cause motor deficits in vivo. Hum Mol Genet 2010; 19:671–683.PubMedCrossRefGoogle Scholar
  66. 65.
    Johnson BS, McCaffery JM, Lindquist S et al. A yeast TDP-43 proteinopathy model: exploring the molecular determinants of TDP-43 aggregation and cellular toxicity. Proc Natl Acad Sci USA 2008; 105:6439–6444.PubMedCrossRefGoogle Scholar
  67. 66.
    Zhang YJ, Xu YF, Cook C et al. Aberrant cleavage of TDP-43 enhances aggregation and cellular toxicity. Proc Natl Acad Sci USA 2009; 106:7607–7612.PubMedCrossRefGoogle Scholar
  68. 67.
    Mackenzie IR, Foti D, Woulfe J et al. A typical frontotemporal lobar degeneration with ubiquitin positive, TDP-43-negative neuronal inclusions. Brain 2008; 131:1282–1293.PubMedCrossRefGoogle Scholar
  69. 68.
    Neumann M, Rademakers R, Roeber S et al. A new subtype of frontotemporal lobar degeneration with FUS pathology. Brain 2009; 132(Pt 11):2922–2931.PubMedCrossRefGoogle Scholar
  70. 69.
    Urwin H, Josephs KA, Rohrer JD et al. FUS pathology defines the majority of tau-and TDP-43 negative frontotemporal lobar degeneration. Acta Neuropathol 2010; 120(1):33–41.PubMedCrossRefGoogle Scholar
  71. 70.
    Lagier-Tourenne C, Cleveland DW. Rethinking ALS: the FUS about TDP-43. Cell 2009; 136(6):1001–1004.PubMedCrossRefGoogle Scholar
  72. 71.
    Josephs KA, Whitwell JL, Parisi JE et al. Caudate atrophy on MRI is a characteristic feature of FTLD-FUS. Eur J Neurol 2010 17:969–975.PubMedCrossRefGoogle Scholar
  73. 72.
    Dormann D, Rodde R, Edbauer D et al. ALS-associated fused in sarcoma (FUS) mutations disrupt transportin-mediated nuclear import. EMBO J 2010; 29:2841–2857.PubMedCrossRefGoogle Scholar
  74. 73.
    Bedford MT, Clarke SG. Protein arginine methylation in mammals: who, what and why. Mol Cell 2009; 33:1–13.PubMedCrossRefGoogle Scholar
  75. 74.
    Mackenzie IR, Neumann M, Bigio EH et al. Nomenclature for neuropathologic subtypes of frontotemporal lobar degeneration: consensus recommendations. Acta Neuropathol 2009; 117(1):15–18.PubMedCrossRefGoogle Scholar
  76. 75.
    Holm IE, Englund E, Mackenzie IRA et al. A reassessment of the neuropathology of frontotemporal dementia linked to chromosome 3 (FTD-3). J Neuropathol Exp Neurol 2007; 66:884–889.PubMedCrossRefGoogle Scholar
  77. 76.
    Holm IE, Isaacs A, Mackenzie IR. Absence of FUS-immunoreactive pathology in frontotemporal dementia linked to chromosome 3 (FTD-3) caused by mutation in the CHMP2B gene. Acta Neuropathol 2009; 118:719–720.PubMedCrossRefGoogle Scholar
  78. 77.
    Urwin H, Ghazi-Noori S, Collinge J et al. The role of CHMP2B in frontotemporal dementia. Biochem Soc Trans 2009; 37:208–212.PubMedCrossRefGoogle Scholar
  79. 78.
    Rohrer JD, Guerreiro R, Vandrovcova J et al. Neurology 2009; 73(18):1451–1456PubMedCrossRefGoogle Scholar
  80. 79.
    Lynch T, Sano M, Marder KS et al. Clinical characteristics of a family with chromosome 17-linked disinhibition-dementia-parkinsonism-amyotrophy complex. Neurology 1994; 44:1878–1884.PubMedGoogle Scholar
  81. 80.
    Spillantini MG, Murrell JR, Goedert M et al. Mutation in the tau gene in familial multiple system tauopathy with presenile dementia. Proc Natl Acad Sci USA 1998; 95:7737–7741.PubMedCrossRefGoogle Scholar
  82. 81.
    Baker M, Mackenzie IR, Pickering-Brown SM et al. Mutations in progranulin cause tau-negative frontotemporal dementia linked to chromosome 17. Nature 2006; 442:916–919.PubMedCrossRefGoogle Scholar
  83. 82.
    D’Souza I, Poorkaj P, Hong M et al. Missense and silent tau gene mutations cause frontotemporal dementia with parkinsonism-chromosome 17 type, by affecting multiple alternative RNA splicing regulatory elements. Proc Natl Acad Sci USA 1999; 96:5598–5603.CrossRefGoogle Scholar
  84. 83.
    Seelaar H, Kamphorst W, Rosso SM et al. Distinct genetic forms of frontotemporal dementia. Neurology 2008; 71:1220–1226.PubMedCrossRefGoogle Scholar
  85. 84.
    Bird T, Nochlin D, Poorkaj P et al. A clinical pathological comparison of three families with frontotemporal dementia and identical mutations in the tau gene (P301L). Brain 1999; 122 (Pt 4):741–756.PubMedCrossRefGoogle Scholar
  86. 85.
    Baker M, Litvan I, Houlden H et al. Association of an extended haplotype in the tau gene with progressive supranuclear palsy. Hum Mol Genet 1999; 8:711–715PubMedCrossRefGoogle Scholar
  87. 86.
    Borroni B, Yancopoulou D, Tsutsui M et al. Association between tau H2 haplotype and age at onset in frontotemporal dementia. Arch Neurol 2005; 62(9):1419–1422.PubMedCrossRefGoogle Scholar
  88. 87.
    Borroni B, Perani D, Agosti C et al. Tau haplotype influences cerebral perfusion pattern in frontotemporal lobar degeneration and related disorders. Acta Neurol Scand 2008; 117(5):359–366.PubMedCrossRefGoogle Scholar
  89. 88.
    Baba Y, Tsuboi Y, Baker MC et al. The effect of tau genotype on clinical features in FTDP-17. Parkinsonism Relat Disord 2005; 11(4):205–208.PubMedCrossRefGoogle Scholar
  90. 89.
    Boeve BF, Tremont-Lukats I, Waclawik A et al. Longitudinal characterization of two siblings with frontotemporal dementia and parkinsonism linked to chromosome 17 associated with the S305N tau mutation. Brain 2005; 128 (pt 4):752–772.PubMedCrossRefGoogle Scholar
  91. 90.
    He Z, Bateman A. Progranulin (granulin-epithelin precursor, PC-cell-derived growth factor, acrogranin) mediates tissue repair and tumorigenesis. J Mol Med 2003; 81:600–612.PubMedCrossRefGoogle Scholar
  92. 91.
    Ahmed Z, Mackenzie IR, Hutton ML et al. Progranulin in frontotemporal lobar degeneration and neuroinflammation. J Neuroinflammation 2007; 4:7.PubMedCrossRefGoogle Scholar
  93. 92.
    Van Damme P, Van Hoecke A, Lambrechts D et al. Progranulin functions as a neurotrophic factor to regulate neurite outgrowth and enhance neuronal survival. J Cell Biol 2008; 181:37–41.PubMedCrossRefGoogle Scholar
  94. 93.
    Hrabal R et al. The hairpin stack fold, a novel protein architecture for a new family of protein growth factors. Nat Struct Biol 1996; 3:747–752.PubMedCrossRefGoogle Scholar
  95. 94.
    Cruts M, Van Broeckhoven C. Loss of progranulin function in frontotemporal lobar degeneration. Trends Genet 2008; 24:186–194.PubMedCrossRefGoogle Scholar
  96. 95.
    Yu CE, Bird TD, Bekris LM et al. The spectrum of mutations in progranulin. Arch Neurol 2010; 67(2):161–170.PubMedCrossRefGoogle Scholar
  97. 96.
    Chen-Plotkin AS, Geser F, Plotkin JB et al. Variations in the progranulin gene affect global gene expression in frontotemporal lobar degeneration. Hum Mol Genet 2008; 17:1349–1362.PubMedCrossRefGoogle Scholar
  98. 97.
    van Swieten JC, Heutink P. Mutations in progranulin (GRN) within the spectrum of clinical and pathological phenotypes of frontotemporal dementia. Lancet Neurol 2008; 7:965–974.PubMedCrossRefGoogle Scholar
  99. 98.
    Le Ber I, van der Zee J, Hannequin D et al. Progranulin null mutations in both sporadic and familial frontotemporal dementia. Hum Mutat 2007; 28:846–855.PubMedCrossRefGoogle Scholar
  100. 99.
    Lopez de Munain A, Alzualde A, Gorostidi A et al. Mutations in progranulin gene: clinical, pathological and ribonucleic acid expression findings. Biol Psychiatry 2008; 63:946–952.PubMedCrossRefGoogle Scholar
  101. 100.
    Gijselinck I, Van Broeckhoven C, Cruts M. Granulin mutations associated with frontotemporal lobar degeneration and related disorders: an update. Hum Mutat 2008; 29(12):1373–1386.PubMedCrossRefGoogle Scholar
  102. 101.
    Borroni B, Archetti S, Alberici A et al. Progranulin genetic variations in frontotemporal lobar degeneration: evidence for low mutation frequency in an Italian clinical series. Neurogenetics 2008; 9:197–205.PubMedCrossRefGoogle Scholar
  103. 102.
    Le Ber I, Camuzat A, Hannequin D et al. Phenotype variability in progranulin mutation carriers: a clinical, neuropsychological, imaging and genetic study. Brain 2008; 131:732–746.PubMedCrossRefGoogle Scholar
  104. 103.
    Beck J, Rohrer JD, Campbell T et al. A distinct clinical, neuropsychological and radiological phenotype is associated with progranulin gene mutations in a large UK series. Brain 2008; 131:706–720.PubMedCrossRefGoogle Scholar
  105. 104.
    Watts GD, Wymer J, Kovach MJ et al. Inclusion body myopathy associated with Paget disease of bone and frontotemporal dementia is caused by mutant valosin-containing protein. Nat Genet 2004; 36:377–381.PubMedCrossRefGoogle Scholar
  106. 105.
    Kimonis VE, Mehta SG, Fulchiero EC et al. Clinical studies in familial VCP myopathy associated with Paget disease of bone and frontotemporal dementia. Am J Med Genet A 2008; 146A:745–757.PubMedCrossRefGoogle Scholar
  107. 106.
    Borroni B, Archetti S, Del Bo R et al. TARDBP Mutations in Frontotemporal Lobar Degeneration: Frequency, Clinical Features and Disease Course. Rejuvenation Res 2010; (ahead of print).Google Scholar
  108. 107.
    Borroni B, Bonvicini C, Alberici A et al. Mutation within TARDBP leads to frontotemporal dementia without motor neuron disease. Hum Mutat 2009; 30:E974–E983.PubMedCrossRefGoogle Scholar
  109. 108.
    Benajiba L, Le Ber I, Camuzat A et al. TARDBP mutations in motoneuron disease with frontotemporal lobar degeneration. Ann Neurol 2009; 65:470–473.PubMedCrossRefGoogle Scholar
  110. 109.
    Kovacs GG, Murrell JR, Horvath S et al. TARDBP variation associated with frontotemporal dementia, supranuclear gaze palsy and chorea. Mov Disord 2009; 24:1843–1847.PubMedCrossRefGoogle Scholar
  111. 110.
    Blair IP, Williams KL, Warraich ST et al. FUS mutations in amyotrophic lateral sclerosis: clinical, pathological, neurophysiological and genetic analysis. J Neurol Neurosurg Psychiatry 2009; 81:639–641.PubMedCrossRefGoogle Scholar
  112. 111.
    Ticozzi N, Silani V, LeClerc AL et al. Analysis of FUS gene mutation in familial amyotrophic lateral sclerosis within an Italian cohort. Neurology 2009; 73:1180–1185.PubMedCrossRefGoogle Scholar
  113. 112.
    Van Deerlin V, Martinez-Lage M, Hakonarson H et al. Genome-wide association study of frontotemporal lobar degeneration with or without concomitant motor neuron disease and TDP-43 neuropathology. 6th International Conference on Frontotemporal Dementias 2008; Rotterdam.Google Scholar
  114. 113.
    Vance C, Al-Chalabi A, Ruddy D et al. Familial amyotrophic lateral sclerosis with frontotemporal dementia is linked to a locus on chromosome 9p13.2-21.3. Brain 2006; 129:868–876.PubMedCrossRefGoogle Scholar
  115. 114.
    Van Deerlin VM, Sleiman PM, Martinez-Lage M et al. Common variants at 7p21 are associated with frontotemporal lobar degeneration with TDP-43 inclusions. Nat Genet 2010; 42(3):234–239.PubMedCrossRefGoogle Scholar
  116. 115.
    Perry RJ, Miller BL. Behavior and treatment in frontotemporal dementia. Neurology 2001; 56 (Suppl 4):S46–S51.PubMedGoogle Scholar
  117. 116.
    Procter AW, Qume M, Francis PT. Neurochemical features offrontotemporal dementia. Dement Geriatr Cog Disord 1999; 10 (suppl 1): 80–84.CrossRefGoogle Scholar
  118. 117.
    Franceschi M, Anchisi D, Pelati O et al. Glucose metabolism and serotonin receptors in the frontotemporal lobe degeneration. Ann Neurol 2005; 57:216–225.PubMedCrossRefGoogle Scholar
  119. 118.
    Huey ED, Putnam KT, Grafman J. A systematic review of neurotransmitter deficits and treatments in frontotemporal dementia. Neurology 2006; 66:17–22.PubMedCrossRefGoogle Scholar
  120. 119.
    Moretti R, Torre P, Antonello RM et al. Olanzapine as a treatment of neuropsychiatric disorders of Alzheimer’s disease and other dementias: a 24-month follow-up of 68 patients. Am J Alzheimers Dis Other Demen 2003; 18:205–214.PubMedCrossRefGoogle Scholar
  121. 120.
    Pijnenburg YA, Sampson EL, Harvey RJ et al. Vulnerability to neuroleptic side effects in frontotemporal lobar degeneration. Int J Geriatr Psychiatry 2003; 18:67–72.PubMedCrossRefGoogle Scholar
  122. 121.
    Hansen LA, Deteresa R, Tobias H et al. Neocortical morphometry and cholinergic neurochemistry in Pick’s disease. Am J Pathol 1988; 131:507–518.PubMedGoogle Scholar
  123. 122.
    Mendez MF, Shapira JS, McMurtray A et al. Preliminary findings: behavioral worsening on donepezil in patients with frontotemporal dementia. Am J Geriatr Psychiatry 2007; 15(1):84–87.PubMedCrossRefGoogle Scholar
  124. 123.
    Swanberg MM. Memantine for behavioral disturbances in frontotemporal dementia: a case series. Alzheimer Dis Assoc Disord 2007; 21:164–166.PubMedCrossRefGoogle Scholar
  125. 124.
    Borroni B, Alberici A, Archetti S et al. New insights into biological markers of frontotemporal lobar degeneration spectrum. Curr Med Chem 2010; 17(10):1002–1009.PubMedCrossRefGoogle Scholar
  126. 125.
    Mioshi E, Hsieh S, Savage S et al. Clinical staging and disease progression in frontotemporal dementia. Neurology 2010; 74(20):1591–1597.PubMedCrossRefGoogle Scholar
  127. 126.
    Trojanowski JQ, Duff K, Fillit H et al. New directions for frontotemporal dementia drug discovery. Frontotemporal Dementia (FTD) Working Group on FTD Drug Discovery. Alzheimers Dement 2008; 4(2):89–93.PubMedCrossRefGoogle Scholar
  128. 127.
    Knopman DS, Kramer JH, Boeve BF et al. Development of methodology for conducting clinical trials in frontotemporal lobar degeneration. Brain 2008; 131:2957–2968.PubMedCrossRefGoogle Scholar

Copyright information

© Landes Bioscience and Springer Science+Business Media 2012

Authors and Affiliations

  • Enrico Premi
    • 1
  • Alessandro Padovani
    • 1
  • Barbara Borroni
    • 1
  1. 1.Centre for Ageing Brain and Neurodegenerative Disorders, Neurology UnitUniversity of BresciaBresciaItaly

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