Acta Neuropathologica

, Volume 120, Issue 1, pp 55–66 | Cite as

Phosphorylated TDP-43 pathology and hippocampal sclerosis in progressive supranuclear palsy

  • Osamu Yokota
  • Yvonne Davidson
  • Eileen H. Bigio
  • Hideki Ishizu
  • Seishi Terada
  • Tetsuaki Arai
  • Masato Hasegawa
  • Haruhiko Akiyama
  • Stephen Sikkink
  • Stuart Pickering-Brown
  • David M. A. MannEmail author
Original Paper


TDP-43 is characteristically accumulated in TDP-43 proteinopathies such as frontotemporal lobar degeneration and motor neurone disease, but is also present in some tauopathies, including Alzheimer’s disease, argyrophilic grain disease, and corticobasal degeneration (CBD). However, several studies have suggested that cases of progressive supranuclear palsy (PSP) lack TDP-43 pathology. We have therefore examined limbic regions of the brain in 19 PSP cases, as well as in 12 CBD cases, using phosphorylation-dependent anti-TDP-43 antibodies. We observed TDP-43-positive inclusions in five PSP cases (26%), as well as in two CBD cases (17%). The amygdala and hippocampal dentate gyrus were most frequently affected in PSP. Regional tau burden tended to be higher in TDP-43-positive PSP cases, and a significant correlation between tau and TDP-43 burden was noted in the occipitotemporal gyrus. Hippocampal sclerosis (HS) was found in 3/5 TDP-43-positive PSP cases, but HS was significantly more frequent in TDP-43-positive than TDP-43 negative PSP cases. Dementia was present in 13/19 (58%) of the PSP cases, in 4/5 TDP-43-positive cases, in all 3 TDP-43-positive cases with HS, in 1/2 TDP-43-positive cases without HS, and 7/14 cases lacking both. TDP-43 and tau were frequently colocalized in the amygdala, but not in the hippocampal dentate gyrus. Immunoblotting demonstrated the characteristic (for TDP-43 proteinopathies) 45 and 25 kDa bands and high molecular weight smear in the TDP-43-positive PSP case. These findings suggest that (1) although PSP is nominally a tauopathy, pathological TDP-43 can accumulate in the limbic system in some cases, and (2) TDP-43 pathology may be concurrent with HS.


Argyrophilic grains Hippocampal sclerosis Progressive supranuclear palsy Tau TDP-43 



This study was supported in part by a research grant from the Uehara Memorial Foundation and Grant No. AG13854 from the National Institutes of Health. We thank Ms. M. Onbe (Department of Neuropsychiatry. Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences) for their excellent technical assistance, and the Parkinson’s Disease Society Brain Bank for making available tissue samples for this study. A part of this study was presented at the 111th annual meeting of the British Neuropathological Society in January 2010.


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Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • Osamu Yokota
    • 1
    • 4
  • Yvonne Davidson
    • 1
  • Eileen H. Bigio
    • 3
  • Hideki Ishizu
    • 4
    • 5
  • Seishi Terada
    • 4
  • Tetsuaki Arai
    • 6
  • Masato Hasegawa
    • 7
  • Haruhiko Akiyama
    • 6
  • Stephen Sikkink
    • 2
  • Stuart Pickering-Brown
    • 2
  • David M. A. Mann
    • 1
    Email author
  1. 1.Neurodegeneration and Mental Health Research Group, Faculty of Medical and Human Sciences, School of Community Based Medicine, Greater Manchester Neurosciences Centre, Hope HospitalUniversity of ManchesterSalfordUK
  2. 2.Neurodegeneration and Mental Health Research Group, Faculty of Medical and Human Sciences, School of Community Based Medicine, A V Hill BuildingUniversity of ManchesterManchesterUK
  3. 3.Department of PathologyNorthwestern University Feinberg School of MedicineChicagoUSA
  4. 4.Department of NeuropsychiatryOkayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesOkayamaJapan
  5. 5.Zikei Institute of PsychiatryOkayamaJapan
  6. 6.Department of PsychogeriatricsTokyo Institute of PsychiatryTokyoJapan
  7. 7.Department of Molecular NeurobiologyTokyo Institute of PsychiatryTokyoJapan

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