Frontotemporal Degeneration

  • Jill S. GoldmanEmail author


The frontotemporal degenerations (FTDs) are a group of neurodegenerative disorders causing dementia with or without other neurological symptoms (ALS and parkinsonism). The most common presentations are behavioral variant frontotemporal dementia with personality/mood changes and primary progressive aphasia. Approximately 40 % of FTD cases have some family history of neurological disease, with about 10 % having an autosomal dominant pattern. The 3 most common FTD genes are MAPT, GRN, and C9orf72. The age of onset and presentation of the FTDs are highly variable even within families. Capacity to consent and family dysfunction add to the complexity of counseling for these disorders.


Amyotrophic Lateral Sclerosis Progressive Supranuclear Palsy Progressive Supranuclear Palsy Primary Progressive Aphasia Presymptomatic Testing 
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Supplementary material

Frontotemporal degeneration (FTD) part 1 (MOV 296915 kb)

Frontotemporal degeneration (FTD) part 2 (MOV 371601 kb)


  1. 1.
    Seelaar, H., Rohrer, J. D., Pijnenburg, Y. A., Fox, N. C., & van Swieten, J. C. (2011). Clinical, genetic and pathological heterogeneity of frontotemporal dementia: a review. Journal of Neurology, Neurosurgery, and Psychiatry, 82(5), 476–486.PubMedCrossRefGoogle Scholar
  2. 2.
    Rabinovici, G. D., & Miller, B. L. (2010). Frontotemporal lobar degeneration: epidemiology, pathophysiology, diagnosis and management. CNS Drugs, 24(5), 375–398.PubMedCentralPubMedCrossRefGoogle Scholar
  3. 3.
    Josephs, K. A., Hodges, J. R., Snowden, J. S., Mackenzie, I. R., Neumann, M., Mann, D. M., et al. (2011). Neuropathological background of phenotypical variability in frontotemporal dementia. Acta Neuropathologica, 122(2), 137–153.PubMedCentralPubMedCrossRefGoogle Scholar
  4. 4.
    Goldman, J. S., Rademakers, R., Huey, E. D., Boxer, A. L., Mayeux, R., Miller, B. L., et al. (2011). An algorithm for genetic testing of frontotemporal lobar degeneration. Neurology, 76(5), 475–483.PubMedCentralPubMedCrossRefGoogle Scholar
  5. 5.
    Rascovsky, K., Hodges, J. R., Knopman, D., Mendez, M. F., Kramer, J. H., Neuhaus, J., et al. (2011). Sensitivity of revised diagnostic criteria for the behavioural variant of frontotemporal dementia. Brain, 134(Pt 9), 2456–2477.PubMedCentralPubMedCrossRefGoogle Scholar
  6. 6.
    Manoochehri, M., & Huey, E. D. (2012). Diagnosis and management of behavioral issues in frontotemporal dementia. Current Neurology and Neuroscience Reports, 12(5), 528–536.PubMedCentralPubMedCrossRefGoogle Scholar
  7. 7.
    Rohrer, J. D., Guerreiro, R., Vandrovcova, J., Uphill, J., Reiman, D., Beck, J., et al. (2009). The heritability and genetics of frontotemporal lobar degeneration. Neurology, 73(18), 1451–1456.PubMedCentralPubMedCrossRefGoogle Scholar
  8. 8.
    Le Ber, I., van der Zee, J., Hannequin, D., Gijselinck, I., Campion, D., Puel, M., et al. (2007). Progranulin null mutations in both sporadic and familial frontotemporal dementia. Human Mutation, 28(9), 846–855.PubMedCrossRefGoogle Scholar
  9. 9.
    Pickering-Brown, S. M., Rollinson, S., Du Plessis, D., Morrison, K. E., Varma, A., Richardson, A. M., et al. (2008). Frequency and clinical characteristics of progranulin mutation carriers in the Manchester frontotemporal lobar degeneration cohort: comparison with patients with MAPT and no known mutations. Brain, 131(Pt 3), 721–731.PubMedCrossRefGoogle Scholar
  10. 10.
    Majounie, E., Renton, A. E., Mok, K., Dopper, E. G., Waite, A., Rollinson, S., et al. (2012). Frequency of the C9orf72 hexanucleotide repeat expansion in patients with amyotrophic lateral sclerosis and frontotemporal dementia: a cross-sectional study. Lancet Neurology, 11(4), 323–330.PubMedCentralCrossRefGoogle Scholar
  11. 11.
    Dejesus-Hernandez, M., Mackenzie, I. R., Boeve, B. F., Boxer, A. L., Baker, M., Rutherford, N. J., et al. (2011). Expanded GGGGCC hexanucleotide repeat in noncoding region of C9ORF72 causes chromosome 9p-linked FTD and ALS. Neuron, 72(2), 245–256.PubMedCentralPubMedCrossRefGoogle Scholar
  12. 12.
    Le Ber, I., Camuzat, A., Guillot-Noel, L., Hannequin, D., Lacomblez, L., Golfier, V., et al. (2013). C9ORF72 repeat expansions in the frontotemporal dementias spectrum of diseases: a flow-chart for genetic testing. Journal of Alzheimer’s Disease, 34(2), 485–499.PubMedGoogle Scholar
  13. 13.
    Hsiung, G. Y., DeJesus-Hernandez, M., Feldman, H. H., Sengdy, P., Bouchard-Kerr, P., Dwosh, E., et al. (2012). Clinical and pathological features of familial frontotemporal dementia caused by C9ORF72 mutation on chromosome 9p. Brain, 135(Pt 3), 709–722.PubMedCentralPubMedCrossRefGoogle Scholar
  14. 14.
    Simón-Sánchez, J., Dopper, E. G., Cohn-Hokke, P. E., Hukema, R. K., Nicolaou, N., Seelaar, H., et al. (2012). The clinical and pathological phenotype of C9ORF72 hexanucleotide repeat expansions. Brain, 135(Pt 3), 723–735.PubMedCrossRefGoogle Scholar
  15. 15.
    Boeve, B. F., Boylan, K. B., Graff-Radford, N. R., DeJesus-Hernandez, M., Knopman, D. S., Pedraza, O., et al. (2012). Characterization of frontotemporal dementia and/or amyotrophic lateral sclerosis associated with the GGGGCC repeat expansion in C9ORF72. Brain, 135(Pt 3), 765–783.PubMedCentralPubMedCrossRefGoogle Scholar
  16. 16.
    Mann, D. M., Rollinson, S., Robinson, A., Bennion Callister, J., Thompson, J. C., Snowden, J. S., et al. (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 Neuropathologica Communications, 1(1), 68.PubMedCentralPubMedCrossRefGoogle Scholar
  17. 17.
    Kimonis, V. E., Fulchiero, E., Vesa, J., & Watts, G. (2008). VCP disease associated with myopathy, Paget disease of bone and frontotemporal dementia: review of a unique disorder. Biochimica et Biophysica Acta, 1782(12), 744–748.PubMedCrossRefGoogle Scholar
  18. 18.
    Gydesen, S., Brown, J. M., Brun, A., Chakrabarti, L., Gade, A., Johannsen, P., et al. (2002). Chromosome 3 linked frontotemporal dementia (FTD-3). Neurology, 59(10), 1585–1594.PubMedCrossRefGoogle Scholar
  19. 19.
    Benajiba, L., Le Ber, I., Camuzat, A., Lacoste, M., Thomas-Anterion, C., Couratier, P., et al. (2009). TARDBP mutations in motoneuron disease with frontotemporal lobar degeneration. Annals of Neurology, 65(4), 470–473.PubMedCrossRefGoogle Scholar
  20. 20.
    Van Langenhove, T., van der Zee, J., Sleegers, K., Engelborghs, S., Vandenberghe, R., Gijselinck, I., et al. (2010). Genetic contribution of FUS to frontotemporal lobar degeneration. Neurology, 74(5), 366–371.PubMedCrossRefGoogle Scholar
  21. 21.
    Vengoechea, J., David, M. P., Yaghi, S. R., Carpenter, L., & Rudnicki, S. A. (2013). Clinical variability and female penetrance in X-linked familial FTD/ALS caused by a P506S mutation in UBQLN2. Amyotroph Lateral Scler Frontotemporal Degener, 14(7–8), 615–619.PubMedCrossRefGoogle Scholar
  22. 22.
    Rademakers, R., Neumann, M., & Mackenzie, I. R. (2012). Advances in understanding the molecular basis of frontotemporal dementia. Nature Reviews. Neurology, 8(8), 423–434.PubMedCentralPubMedGoogle Scholar
  23. 23.
    Nalbandian, A., Donkervoort, S., Dec, E., Badadani, M., Katheria, V., Rana, P., et al. (2011). The multiple faces of valosin-containing protein-associated diseases: inclusion body myopathy with Paget’s disease of bone, frontotemporal dementia, and amyotrophic lateral sclerosis. Journal of Molecular Neuroscience, 45(3), 522–531.PubMedCrossRefGoogle Scholar
  24. 24.
    Synofzik, M., Born, C., Rominger, A., Lummel, N., Schöls, L., Biskup, S., et al. (2013). Targeted high-throughput sequencing identifies a TARDBP mutation as a cause of early-onset FTD without motor neuron disease. Neurobiol Aging.Google Scholar
  25. 25.
    Huey, E. D., Ferrari, R., Moreno, J. H., Jensen, C., Morris, C. M., Potocnik, F., et al. (2012). FUS and TDP43 genetic variability in FTD and CBS. Neurobiology of Aging, 33(5), 1016.e9–17.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  1. 1.Taub Institute, Columbia University Medical CenterNew YorkUSA

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