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 W Dickson, Zbigniew K WszolekTakeshi Iwatsubo, Stuart M. Pickering-Brown, Janice Holton, Andrew Lees, Tamas Revesz, David M A Mann

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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.

Original languageEnglish (US)
Pages (from-to)329-340
Number of pages12
JournalActa Neuropathologica
Volume111
Issue number4
DOIs
StatePublished - Apr 2006

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Frontotemporal Lobar Degeneration
Monoclonal Antibodies
Protein Isoforms
Neurofibrillary Tangles
Mutation
Pathology
Apraxias
Frontotemporal Dementia
Microtubule-Associated Proteins
Neuroglia
Exons
Immunohistochemistry

ASJC Scopus subject areas

  • Clinical Neurology
  • Pathology and Forensic Medicine
  • Neuroscience(all)

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An immunohistochemical study of cases of sporadic and inherited frontotemporal lobar degeneration using 3R- and 4R-specific tau monoclonal antibodies. / de Silva, Rohan; Lashley, Tammaryn; Strand, Catherine; Shiarli, Anna Maria; Shi, Jing; Tian, Jinzhou; Bailey, Kathryn L.; Davies, Peter; Bigio, Eileen H.; Arima, Kunimasa; Iseki, Eizo; Murayama, Shigeo; Kretzschmar, Hans; Neumann, Manuela; Lippa, Carol; Halliday, Glenda; MacKenzie, James; Ravid, Rivka; Dickson, Dennis W; Wszolek, Zbigniew K; Iwatsubo, Takeshi; Pickering-Brown, Stuart M.; Holton, Janice; Lees, Andrew; Revesz, Tamas; Mann, David M A.

In: Acta Neuropathologica, Vol. 111, No. 4, 04.2006, p. 329-340.

Research output: Contribution to journalArticle

de Silva, R, Lashley, T, Strand, C, Shiarli, AM, Shi, J, Tian, J, Bailey, KL, Davies, P, Bigio, EH, Arima, K, Iseki, E, Murayama, S, Kretzschmar, H, Neumann, M, Lippa, C, Halliday, G, MacKenzie, J, Ravid, R, Dickson, DW, Wszolek, ZK, Iwatsubo, T, Pickering-Brown, SM, Holton, J, Lees, A, Revesz, T & Mann, DMA 2006, 'An immunohistochemical study of cases of sporadic and inherited frontotemporal lobar degeneration using 3R- and 4R-specific tau monoclonal antibodies', Acta Neuropathologica, vol. 111, no. 4, pp. 329-340. https://doi.org/10.1007/s00401-006-0048-x
de Silva, Rohan ; Lashley, Tammaryn ; Strand, Catherine ; Shiarli, Anna Maria ; Shi, Jing ; Tian, Jinzhou ; Bailey, Kathryn L. ; Davies, Peter ; Bigio, Eileen H. ; Arima, Kunimasa ; Iseki, Eizo ; Murayama, Shigeo ; Kretzschmar, Hans ; Neumann, Manuela ; Lippa, Carol ; Halliday, Glenda ; MacKenzie, James ; Ravid, Rivka ; Dickson, Dennis W ; Wszolek, Zbigniew K ; Iwatsubo, Takeshi ; Pickering-Brown, Stuart M. ; Holton, Janice ; Lees, Andrew ; Revesz, Tamas ; Mann, David M A. / An immunohistochemical study of cases of sporadic and inherited frontotemporal lobar degeneration using 3R- and 4R-specific tau monoclonal antibodies. In: Acta Neuropathologica. 2006 ; Vol. 111, No. 4. pp. 329-340.
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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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T1 - An immunohistochemical study of cases of sporadic and inherited frontotemporal lobar degeneration using 3R- and 4R-specific tau monoclonal antibodies

AU - de Silva, Rohan

AU - Lashley, Tammaryn

AU - Strand, Catherine

AU - Shiarli, Anna Maria

AU - Shi, Jing

AU - Tian, Jinzhou

AU - Bailey, Kathryn L.

AU - Davies, Peter

AU - Bigio, Eileen H.

AU - Arima, Kunimasa

AU - Iseki, Eizo

AU - Murayama, Shigeo

AU - Kretzschmar, Hans

AU - Neumann, Manuela

AU - Lippa, Carol

AU - Halliday, Glenda

AU - MacKenzie, James

AU - Ravid, Rivka

AU - Dickson, Dennis W

AU - Wszolek, Zbigniew K

AU - Iwatsubo, Takeshi

AU - Pickering-Brown, Stuart M.

AU - Holton, Janice

AU - Lees, Andrew

AU - Revesz, Tamas

AU - Mann, David M A

PY - 2006/4

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N2 - 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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