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01-04-2006 | Original Paper

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

Authors: 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. Mann

Published in: Acta Neuropathologica | Issue 4/2006

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.

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Title: An immunohistochemical study of cases of sporadic and inherited frontotemporal lobar degeneration using 3R- and 4R-specific tau monoclonal antibodies
Authors: 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. Mann
Publication date: 01-04-2006
Publisher: Springer-Verlag
Published in: Acta Neuropathologica / Issue 4/2006
Print ISSN: 0001-6322
Electronic ISSN: 1432-0533
DOI: https://doi.org/10.1007/s00401-006-0048-x

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

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