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Acta Neuropathologica

, Volume 111, Issue 4, pp 329–340 | Cite as

An immunohistochemical study of cases of sporadic and inherited frontotemporal lobar degeneration using 3R- and 4R-specific tau monoclonal antibodies

  • Rohan de Silva
  • Tammaryn Lashley
  • Catherine Strand
  • Anna-Maria Shiarli
  • Jing Shi
  • Jinzhou Tian
  • Kathryn L. Bailey
  • Peter Davies
  • Eileen H. Bigio
  • Kunimasa Arima
  • Eizo Iseki
  • Shigeo Murayama
  • Hans Kretzschmar
  • Manuela Neumann
  • Carol Lippa
  • Glenda Halliday
  • James MacKenzie
  • Rivka Ravid
  • Dennis Dickson
  • Zbigniew Wszolek
  • Takeshi Iwatsubo
  • Stuart M. Pickering-Brown
  • Janice Holton
  • Andrew Lees
  • Tamas Revesz
  • David M. A. MannEmail author
Original Paper

Abstract

The pathological distinctions between the various clinical and pathological manifestations of frontotemporal lobar degeneration (FTLD) remain unclear. Using monoclonal antibodies specific for 3- and 4-repeat isoforms of the microtubule associated protein, tau (3R- and 4R-tau), we have performed an immunohistochemical study of the tau pathology present in 14 cases of sporadic forms of FTLD, 12 cases with Pick bodies and two cases without and in 27 cases of familial FTLD associated with 12 different mutations in the tau gene (MAPT), five cases with Pick bodies and 22 cases without. In all 12 cases of sporadic FTLD where Pick bodies were present, these contained only 3R-tau isoforms. Clinically, ten of these cases had frontotemporal dementia and two had progressive apraxia. Only 3R-tau isoforms were present in Pick bodies in those patients with familial FTLD associated with L266V, Q336R, E342V, K369I or G389R MAPT mutations. Patients with familial FTLD associated with exon 10 N279K, N296H or +16 splice site mutations showed tau pathology characterised by neuronal neurofibrillary tangles (NFT) and glial cell tangles that contained only 4R-tau isoforms, as did the NFT in P301L MAPT mutation. With the R406W mutation, NFT contained both 3R- and 4R-tau isoforms. We also observed two patients with sporadic FTLD, but without Pick bodies, in whom the tau pathology comprised only of 4R-tau isoforms. We have therefore shown by immunohistochemistry that different specific tau isoform compositions underlie the various kinds of tau pathology present in sporadic and familial FTLD. The use of such tau isoform specific antibodies may refine pathological criteria underpinning FTLD.

Keywords

Progressive Supranuclear Palsy Progressive Supranuclear Palsy FTLD Case Familial FTLD Sporadic FTLD 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgements

AMS was supported by a Wolfson Scholarship and Alzheimer’s Research Trust Alzheimer’s Disease Research Centre Grant to DMAM. TL is supported by the Parkinson’s Disease Society. This work was supported by the Reta Lila Weston Trust for Medical Research (RdS, AL, TL) and the PSP (Europe) Association (KS), which also support the Queen Square Brain Bank. The authors thank the many other people who were involved in collecting and characterising the familial FTLD cases with MAPT mutations and the other sporadic FTLD cases and by doing so making this multicentre collaborative study possible. The authors would also like to thank the patients and their families, without whose generous support none of this research would have been possible.

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Copyright information

© Springer-Verlag 2006

Authors and Affiliations

  • Rohan de Silva
    • 1
  • Tammaryn Lashley
    • 2
  • Catherine Strand
    • 2
  • Anna-Maria Shiarli
    • 3
  • Jing Shi
    • 3
    • 4
  • Jinzhou Tian
    • 3
    • 4
  • Kathryn L. Bailey
    • 3
  • Peter Davies
    • 5
  • Eileen H. Bigio
    • 6
  • Kunimasa Arima
    • 7
  • Eizo Iseki
    • 8
  • Shigeo Murayama
    • 9
  • Hans Kretzschmar
    • 10
  • Manuela Neumann
    • 10
  • Carol Lippa
    • 11
  • Glenda Halliday
    • 12
  • James MacKenzie
    • 13
  • Rivka Ravid
    • 14
  • Dennis Dickson
    • 15
  • Zbigniew Wszolek
    • 15
  • Takeshi Iwatsubo
    • 16
  • Stuart M. Pickering-Brown
    • 3
    • 15
  • Janice Holton
    • 2
  • Andrew Lees
    • 1
  • Tamas Revesz
    • 2
  • David M. A. Mann
    • 3
    Email author
  1. 1.Reta Lila Weston Institute of Neurological StudiesUniversity College LondonLondonUK
  2. 2.Department of Molecular Neuroscience, Queen Square Brain Bank, Institute of NeurologyUniversity College LondonLondonUK
  3. 3.Centre for Clinical NeurosciencesUniversity of Manchester, Greater Manchester Neurosciences Centre, Hope HospitalSalfordUK
  4. 4.Department of Care of the ElderlyDongzhimen HospitalBeijingP R China
  5. 5.Department of PathologyAlbert Einstein College of MedicineBronxUSA
  6. 6.Northwestern University Alzheimer’s Disease CenterChicagoUSA
  7. 7.National Centre of Neurology and PsychiatryMusashi HospitalTokyoJapan
  8. 8.Juntendo Tokyo Koto Geriatric Medical CenterJuntendo University School of MedicineTokyoJapan
  9. 9.Department of NeuropathologyTokyo Metropolitan Institute of GerontologyTokyoJapan
  10. 10.Reference Centre for Prion Diseases and Neurodegenerative DiseasesInstitute of NeuropathologyMunchenGermany
  11. 11.Memory Disorders CentreDrexel University College of MedicinePhiladelphiaUSA
  12. 12.Department of Neuropathology, Prince of Wales Medical Research InstituteUniversity of New South WalesRandwickAustralia
  13. 13.The Royal Infirmary, ForesterhillAberdeenScotland
  14. 14.Netherlands Brain Bank1105 AZThe Netherlands
  15. 15.Mayo ClinicJacksonvilleUSA
  16. 16.Department of Neuropathology and NeuroscienceUniversity of TokyoTokyoJapan

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