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Fronto-temporal lobar degeneration: neuropathology in 60 cases

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Abstract

Sixty cases of frontotemporal lobar degeneration (FTLD) were collected over 22 years. Brain weight was negatively correlated with disease duration. The neuronal and/or glial inclusions were labeled by anti-TDP, anti-FUS or anti-TAU antibodies, respectively, in 40, 3 and 12 cases. In the FTLD-TDP group, mutation of the progranulin gene was found in four cases (FTD-GRN), with nuclear, cat eye inclusions and severe neuronal loss in CA1 and subiculum. The motor neurons were involved in 27 cases (fronto-temporal dementia with amyotrophic lateral sclerosis = FTD-ALS). Familial FTD-ALS cases lived longer than sporadic ones. In nine cases, there was no ALS, no GRN mutation (FTD-NAP). The cases in the FTD-ALS and FTD-NAP subgroups were of Sampathu type 2 (TDP-positive inclusions located mostly in cell bodies and short neurites) with the exception of five cases which belonged to type 1 (long TDP-positive neurites in the superficial layers of the cortex). All of the FTLD-FUS of this series cases were affected by neuronal intermediate filament inclusion disease (NIFID). They were young. The survival was short. In the FTLD-tau group, mutations P301P (previously not recognized as pathogenic), P301L and S305N were identified. Pick disease (n = 5) appeared as a homogeneous sporadic disorder. The current nomenclature allows the neuropathological classification of nearly all the cases of FTD. The prevalence of the different types of FTD is tightly linked to the recruitment. This series was enriched in motor neuron disease (explaining the overall predominance of type 2 TDP inclusions).

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Acknowledgments

We are grateful to the patients and to the patients’ family. The national Brain Bank GIE Neuro-CEB provided 13 cases of this study. We are grateful to the help of the patients’ associations ARSEP, Connaître les syndromes cérébelleux, France Alzheimer, France Parkinson. The expert work of the technicians of Escourolle laboratory is greatly acknowledged. This work has been partly funded by a research grant from IBISA and by the FTD/FTD-MND network (ANR project).

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Authors and Affiliations

  1. Centre de Recherche de l’Institut du Cerveau et de la Moelle Epinière, INSERM UMR_S975, CNRS UMR7225, Groupe Hospitalier Pitié-Salpêtrière, AP-HP and UPMC-Sorbonne Universités, Paris, France

    Danielle Seilhean, Isabelle Le Ber, Marie Sarazin, Stéphanie Millecamps, Eric LeGuern, Bruno Dubois, Alexis Brice & Charles Duyckaerts

  2. Laboratoire de Neuropathologie, Groupe Hospitalier Pitié-Salpêtrière, AP-HP and UPMC-Sorbonne Universités, Paris, France

    Danielle Seilhean, Jean-Jacques Hauw & Charles Duyckaerts

  3. Fédération des maladies du système nerveux, Groupe Hospitalier Pitié-Salpêtrière, AP-HP and UPMC-Sorbonne Universités, Paris, France

    Isabelle Le Ber, Marie Sarazin, Lucette Lacomblez, François Salachas, Pierre-François Pradat, Nadine Le Forestier, Bruno Dubois & Vincent Meininger

  4. Département de Génétique et Cytogénétique, Unité Fonctionnelle de Neurogénétique moléculaire et cellulaire, Groupe Hospitalier Pitié-Salpêtrière, AP-HP and UPMC-Sorbonne Universités, Paris, France

    Eric LeGuern & Alexis Brice

  5. Centre de référence maladies rares ‘Sclérose Latérale Amyotrophique’, Groupe Hospitalier Pitié-Salpêtrière, AP-HP and UPMC-Sorbonne Universités, Paris, France

    Lucette Lacomblez, François Salachas, Pierre-François Pradat, Nadine Le Forestier & Vincent Meininger

  6. Centre de référence ‘Démences Rares’, Groupe Hospitalier Pitié-Salpêtrière, AP-HP and UPMC-Sorbonne Universités, Paris, France

    Isabelle Le Ber, Marie Sarazin, Bruno Dubois & Alexis Brice

  7. Laboratoire de Neuropathologie Escourolle, 47 Boulevard de l’ Hôpital, 75651, Paris Cedex 13, France

    Charles Duyckaerts

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  1. Danielle Seilhean
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  2. Isabelle Le Ber
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  3. Marie Sarazin
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  4. Lucette Lacomblez
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  5. Stéphanie Millecamps
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  6. François Salachas
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  7. Pierre-François Pradat
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  8. Nadine Le Forestier
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  9. Eric LeGuern
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  10. Bruno Dubois
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  11. Vincent Meininger
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  12. Alexis Brice
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  13. Jean-Jacques Hauw
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  14. Charles Duyckaerts
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Correspondence to Charles Duyckaerts.

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In honor of Professor Kurt Jellinger.

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Seilhean, D., Le Ber, I., Sarazin, M. et al. Fronto-temporal lobar degeneration: neuropathology in 60 cases. J Neural Transm 118, 753–764 (2011). https://doi.org/10.1007/s00702-011-0649-y

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