Acta Neuropathologica

, Volume 117, Issue 4, pp 429–444 | Cite as

Clinicopathological characterization of Pick’s disease versus frontotemporal lobar degeneration with ubiquitin/TDP-43-positive inclusions

  • Osamu Yokota
  • Kuniaki Tsuchiya
  • Tetsuaki Arai
  • Saburo Yagishita
  • Osamu Matsubara
  • Akihide Mochizuki
  • Akira Tamaoka
  • Mitsuru Kawamura
  • Hidetoshi Yoshida
  • Seishi Terada
  • Hideki Ishizu
  • Shigetoshi Kuroda
  • Haruhiko Akiyama
Original Paper


Although frontotemporal lobar degeneration with ubiquitin/TDP-43-positive inclusions (FTLD-TDP) and Pick’s disease are common pathological substrates in sporadic FTLD, clinical differentiation of these diseases is difficult. We performed a retrospective review of medical records and semiquantitative examination of neuronal loss of 20 sporadic FTLD-TDP and 19 Pick’s disease cases. Semantic dementia as the first syndrome developed only in FTLD-TDP patients. Impaired speech output in the early stage was five times more frequent in Pick’s disease than in FTLD-TDP. The total frequency of asymmetric motor disturbances (e.g., parkinsonism, pyramidal signs, and contracture) during the course was significantly more frequent in FTLD-TDP (78%) than in Pick’s disease cases (14%). Asymmetric pyramidal signs were found in 7 of 13 FTLD-TDP cases with corticospinal tract degeneration similar to primary lateral sclerosis. Frontotemporal dementia as the first syndrome was noted in both FTLD-TDP (28%) and Pick’s disease cases (64%); however, only FTLD-TDP cases subsequently developed asymmetric motor disturbances, and some of the cases further exhibited hemineglect. Concordant with these clinical findings, degeneration in the temporal cortex, caudate nucleus, putamen, globus pallidus, substantia nigra, and corticospinal tract was significantly more severe in FTLD-TDP, and degeneration in the frontal cortex tended to be more severe in Pick’s disease. Given these findings, the initial impairment of semantic memory or comprehension and subsequent asymmetric motor disturbances in sporadic FTLD patients predict sporadic FTLD-TDP rather than Pick’s disease, while initial behavioral symptoms or non-fluent aphasia without subsequent asymmetric motor disturbances predict Pick’s disease rather than sporadic FTLD-TDP.


Agnosia Aphasia Caudate nucleus Corticobasal degeneration Motor neuron disease TDP-43 



We would like to thank Ms. C. Haga (Department of Neuropathology, Tokyo Institute of Psychiatry) and Mr. A. Sasaki for help with the production of the manuscript. This work was supported by a grant-in-aid for scientific research from the Ministry of Education, Culture, Sports, Science and Technology (14570957) and a research grant from the Zikei Institute of Psychiatry. This work was supported by a grant-in-aid for scientific research from the Ministry of Education, Culture, Sports, Science and Technology (14570957) and a research grant from the Zikei Institute of Psychiatry.

Supplementary material

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Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • Osamu Yokota
    • 1
    • 2
  • Kuniaki Tsuchiya
    • 1
    • 3
    • 4
  • Tetsuaki Arai
    • 1
  • Saburo Yagishita
    • 5
  • Osamu Matsubara
    • 6
  • Akihide Mochizuki
    • 7
  • Akira Tamaoka
    • 7
  • Mitsuru Kawamura
    • 8
  • Hidetoshi Yoshida
    • 2
  • Seishi Terada
    • 2
  • Hideki Ishizu
    • 2
    • 9
  • Shigetoshi Kuroda
    • 2
  • Haruhiko Akiyama
    • 1
  1. 1.Department of NeuropathologyTokyo Institute of PsychiatryTokyoJapan
  2. 2.Department of NeuropsychiatryOkayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesOkayamaJapan
  3. 3.Department of Laboratory Medicine and PathologyTokyo Metropolitan Matsuzawa HospitalTokyoJapan
  4. 4.Department of NeurologyTokyo Metropolitan Matsuzawa HospitalTokyoJapan
  5. 5.Department of PathologyKanagawa Rehabilitation CenterKanagawaJapan
  6. 6.Department of PathologyNational Defense Medical CollegeSaitamaJapan
  7. 7.Department of Neurology, Doctoral Program in Medical Sciences for Control of Pathological Processes, Graduate School of Comprehensive Human SciencesUniversity of TsukubaIbarakiJapan
  8. 8.Department of NeurologyShowa University School of MedicineTokyoJapan
  9. 9.Department of Laboratory MedicineZikei Institute of PsychiatryOkayamaJapan

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