Skip to main content

Advertisement

SpringerLink
Log in

Frontotemporal dementia, motor neuron disease and tauopathy: clinical and neuropathological study in a family

  • Case Report
  • Published:
Acta Neuropathologica Aims and scope Submit manuscript

Abstract

We report a familial disorder occurring in three patients that presented as frontotemporal dementia (FTD). A neuropathological study was performed in a 58-year-old patient, who developed FTD 2 years prior to the onset of motor neuron disease (MND), and died at age 62. Lesions indicative of associated MND were observed: neuronal loss in the anterior horns of the spinal cord, Bunina bodies, axonal spheroids, degeneration of the pyramidal tracts, and of FTD: decreased neuronal density and laminar microvacuolation of layers II and III in the frontal and temporal cortex. Ubiquitin-only-immunoreactive changes were found in the spinal cord and medulla, but were absent from the temporal and frontal cortex. There were also widespread deposits of various neuronal and glial inclusions containing abnormally phosphorylated tau protein, the Western blotting pattern of which was characterized by two major bands of 64 and 69 kDa. There were no abnormalities of the entire coding sequences of microtubule-associated protein tau (MAPT) and copper-zinc superoxide dismutase (SOD 1 ) genes. Our results suggest that FTD associated with MND can be caused by a larger spectrum of neuropathological lesions than commonly accepted.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1 a
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8

Similar content being viewed by others

References

  1. Basak M, Erturk M, Oflazoglu B, Ozel A, Yildiz GB, Forta H (2002) Magnetic resonance imaging in amyotrophic lateral sclerosis. Acta Neurol Scand 105:395–399

    CAS  PubMed  Google Scholar 

  2. Brooks BR, Miller RG, Swash M, Munsat TL, World Federation of Neurology Research Group on Motor Neuron Diseases (2000) El Escorial revisited. Amyotroph Lateral Scler Other Motor Neuron Disord 1:293–299

    CAS  PubMed  Google Scholar 

  3. Brown J, Ashworth A, Gydesen S, Sorensen A, Hardy J, Collinge J (1995) Familial non-specific dementias maps to chromosome 3. Hum Mol Genet 45:1625–1628

    Google Scholar 

  4. Buée L, Delacourte A (1999) Comparative biochemistry of tau in progressive supranuclear palsy, corticobasal degeneration, FTDP-17 and Pick’s disease. Brain Pathol 9:681–693

    PubMed  Google Scholar 

  5. Dickson DW (ed) (2003) Neurodegeneration: the molecular pathology of dementia and movement disorders. ISN Neuropath Press, Basel, p 414

  6. Dickson DW, Bergeron C, Chin SS, Duyckaerts C, Horoupian D, Ikeda K, Jellinger K, Lantos PL, Lippa CF, Mirra SS, Tabaton M, Vonsattel JP, Wakabayashi K, Litvan I (2002) Office of rare diseases neuropathologic criteria for corticobasal degeneration. J Neuropathol Exp Neurol 61:935–946

    CAS  PubMed  Google Scholar 

  7. Dumanchin C, Camuzat A, Campion D, Verpillat P, Hannequin D, Dubois B, Saugier-Veber P, Martin C, Penet C, Charbonnier F, Agid Y, Frebourg T, Brice A (1998) Segregation of a missense mutation in the microtubule-associated protein tau gene with familial frontotemporal dementia and parkinsonism. Hum Mol Genet 7:1825–1829

    Article  CAS  PubMed  Google Scholar 

  8. Ghetti B, Hutton M, Wszolek ZK (2003) Frontotemporal dementia and parkinsonism linked to chromosome 17 associated with tau gene mutations (FTDP-17) In: Dickson DW (ed) Neurodegeneration: the molecular pathology of dementia and movement disorders. ISN Neuropath Press, Basel, pp 86–102

  9. Gunnarsson LG, Dahlbom K, Strandman E (1991) Motor neuron disease and dementia reported among 13 members of a single family. Acta Neurol Scand 84:429–433

    CAS  PubMed  Google Scholar 

  10. Hauw JJ, Daniel SE, Dickson D, Horoupian DS, Jellinger K, Lantos PL, McKee A, Tabaton M, Litvan I (1994) Preliminary NINDS neuropathologic criteria for Steele-Richardson-Olszewski syndrome (progressive supranuclear palsy) Neurology 44:2015–2019

    Google Scholar 

  11. Heutink P (2000) Untangling tau-related dementia. Hum Mol Genet 9:979–986

    CAS  PubMed  Google Scholar 

  12. Hosler BA, Siddique T, Sapp PC, Sailor W, Huang MC, Hossain A, Daube JR, Nance M, Fan C, Kaplan J, Hung WY, McKenna-Yasek D, Haines JL, Pericak-Vance MA, Horvitz RH, Horvitz RHB Jr (2000) Linkage of familial amyotrophic lateral sclerosis with frontotemporal dementia to chromosome 9q21-q22. JAMA 284:1664–1669

    CAS  PubMed  Google Scholar 

  13. Houlden H, Baker M, Adamson J, Grover A, Waring S, Dickson D, Lynch T, Boeve B, Petersen RC, Pickering-Brown S, Owen F, Neary D, Craufurd D, Snowden J, Mann D, Hutton M (1999) Frequency of tau mutations in three series of non-Alzheimer’s degenerative dementia. Ann Neurol 46:243–248

    CAS  PubMed  Google Scholar 

  14. Hudson AJ (1981) Amyotrophic lateral sclerosis and its association with dementia, parkinsonism, and other neurological disorders : a review. Brain 104:217–247

    CAS  PubMed  Google Scholar 

  15. Hutton M, Lendon CL, Rizzu P, Baker M, Froelich S, Houlden H, Pickering-Brown S, Chakraverty S, Isaacs A, Grover A, et al (1998) Association of missense and 5’-splice-site mutations in tau with the inherited dementia FTDP-17. Nature 393:702–705

    Article  CAS  PubMed  Google Scholar 

  16. Komori T, Arai N, Oda M, Nakayama H, Mori H, Yagishita S, Takahashi T, Amano N, Murayama S, Murakami S, Shibata N, Kobayashi M, Sasaki S, Iwata M (1998) Astrocytic plaques and tufts of abnormal fibers do not coexist in corticobasal degeneration and progressive supranuclear palsy. Acta Neuropathol 96:401–408

    CAS  PubMed  Google Scholar 

  17. Litvan I, Hauw JJ, Bartko JJ, Lantos PL, Daniel SE, Horoupian DS, McKee A, Dickson D, Bancher C, Tabaton M, Jellinger K, Anderson DW (1996) Validity and reliability of the preliminary NINDS neuropathologic criteria for progressive supranuclear palsy and related disorders. J Neuropathol Exp Neurol 55:97–105

    CAS  PubMed  Google Scholar 

  18. Lowe J, Rossor M (2003) Frontotemporal lobar degeneration: In: Dickson DW (ed) Neurodegeneration: the molecular pathology of dementia and movement disorders. ISN Neuropath Press, Basel, pp 342–348

  19. Lynch T, Sano M, Marder KS, Bell KL, Foster NL, Defendini RF, Sima AAF, Keohane C, Nygaard TG, Fahn S, Mayeux R, Rowland LP, Wilhelmsen KC (1994) Clinical characteristics of a family with chromosome 17-linked disinhibition-dementia-parkinsonism-amyotrophy complex. Neurology 44:1878–1884

    CAS  PubMed  Google Scholar 

  20. Mawal-Dewan M, Schmidt ML, Balin B, Perl DP, Lee VM, Trojanowski JQ (1996) Identification of phosphorylation sites in PHF-TAU from patients with Guam amyotrophic lateral sclerosis/parkinsonism-dementia complex. J Neuropathol Exp Neurol 55:1051–1059

    CAS  PubMed  Google Scholar 

  21. Mitsuyama Y (1993) Presenile dementia with motor neuron disease. Dementia 4:137–142

    CAS  PubMed  Google Scholar 

  22. Nakano I (2000) Frontotemporal dementia with motor neuron disease (amyotrophic lateral sclerosis with dementia) Neuropathology 20:68–75

    Google Scholar 

  23. Neary D (1995) Neuropsychological aspects of frontotemporal degeneration. Ann NY Acad Sci 769:15–22

    CAS  PubMed  Google Scholar 

  24. Neary D (1998) Frontotemporal lobar degeneration. A consensus on clinical diagnosis criteria. Neurology 51:1546–1554

    CAS  PubMed  Google Scholar 

  25. Neary D, Snowden JS, Mann DM (2000) Cognitive change in motor neuron disease/amyotrophic lateral sclerosis (MND/ALS) J Neurol Sci 180:15–20

    Google Scholar 

  26. Niizato K, Tsuchiya K, Tominaga I, Kato Y, Ikeda K (1997) Pick’s disease with amyotrophic lateral sclerosis (ALS): report of two autopsy cases and literature review. J Neurol Sci 148:107–112

    Article  CAS  PubMed  Google Scholar 

  27. Paviour DC, Lees AJ, Josephs KA, Ozawa T, Ganguly M, Strand C, Godbolt A, Howard RS, Revesz T, Holton JL (2004) Frontotemporal lobar degeneration with ubiquitin-only-immunoreactive neuronal changes: broadening the clinical picture to include progressive supranuclear palsy. Brain 127:2441–2451

    Article  CAS  PubMed  Google Scholar 

  28. Pinsky L, Finlayson MH, Libman I, Scott BH (1975) Familial amyotrophic lateral sclerosis with dementia: a second Canadian family. Clin Gen 7:186–191

    CAS  Google Scholar 

  29. Siddique T, Nijhawan D, Hentati A (1996) Molecular genetic basis of familial ALS. Neurology 47 (Suppl 2):S27–S35

    CAS  PubMed  Google Scholar 

  30. Wilhelmsen KC (1998) Chromosome 17-linked dementias. Cell Mol Life Sci 54:920–924

    Article  CAS  PubMed  Google Scholar 

  31. Wilhelmsen KC, Forman MS, Rosen HJ, Alving LI, Goldman J, Feiger J, Lee JV, Segall SK, Kramer JH, Lomen-Hoerth C, Rankin KP, Johnson J, Feiler HS, Weiner MW, Lee VM, Trojanowski JQ, Miller BL (2004) 17q-linked frontotemporal dementia-amyotrophic lateral sclerosis without tau mutations with tau and alpha-synuclein inclusions. Arch Neurol 61:398–406

    PubMed  Google Scholar 

  32. Zhang L, Ulug AM, Zimmerman RD, Lin MT, Rubin M, Beal MF (2003) The diagnostic utility of FLAIR imaging in clinically verified amyotrophic lateral sclerosis. J Magn Reson Imaging 17:521–527

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

The authors are grateful to Richard Medeiros, Rouen University Hospital Medical Editor, for his valuable advice in editing the manuscript, and to Siegfried Le Roy for the iconography.

Author information

Authors and Affiliations

  1. Neurology Department, Rouen University Hospital, 1 rue de Germont, 76031, Rouen, France

    O. Martinaud, L. Guyant-Maréchal, P. Ahtoy & D. Hannequin

  2. Neuropathology Laboratory, Rouen University Hospital, Rouen, France

    A. Laquerrière & P. Bourgeois

  3. Quant. I. F. laboratory and Nuclear Medicine Department, Rouen University Hospital, Rouen, France

    P. Vera

  4. Inserm U 422, groupe VCDN, Lille, France

    N. Sergeant

  5. Inserm U 289, University Hospital La Pitié-Salpêtrière, Paris, France

    A. Camuzat

  6. Neuropathology Department, University Hospital La Pitié-Salpêtrière, Paris, France

    J. J. Hauw

  7. Inserm U 614, IFRMP, Faculty of Medecine and Pharmacy, Rouen, France

    D. Campion & D. Hannequin

Authors
  1. O. Martinaud
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. A. Laquerrière
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. L. Guyant-Maréchal
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. P. Ahtoy
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. P. Vera
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. N. Sergeant
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. A. Camuzat
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. P. Bourgeois
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. J. J. Hauw
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. D. Campion
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. D. Hannequin
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to O. Martinaud.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Martinaud, O., Laquerrière, A., Guyant-Maréchal, L. et al. Frontotemporal dementia, motor neuron disease and tauopathy: clinical and neuropathological study in a family. Acta Neuropathol 110, 84–92 (2005). https://doi.org/10.1007/s00401-005-1028-2

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00401-005-1028-2

Keywords

Search

Navigation