TY - JOUR
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
AU - Wszolek, Zbigniew
AU - Iwatsubo, Takeshi
AU - Pickering-Brown, Stuart M.
AU - Holton, Janice
AU - Lees, Andrew
AU - Revesz, Tamas
AU - Mann, David M.A.
N1 - Funding Information:
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.
PY - 2006/4
Y1 - 2006/4
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.
AB - 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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U2 - 10.1007/s00401-006-0048-x
DO - 10.1007/s00401-006-0048-x
M3 - Article
C2 - 16552612
AN - SCOPUS:33645766284
SN - 0001-6322
VL - 111
SP - 329
EP - 340
JO - Acta Neuropathologica
JF - Acta Neuropathologica
IS - 4
ER -