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01-07-2015 | Neurology and Preclinical Neurological Studies - Original Article

Neuropathological assessments of the pathology in frontotemporal lobar degeneration with TDP43-positive inclusions: an inter-laboratory study by the BrainNet Europe consortium

Authors: Irina Alafuzoff, Maria Pikkarainen, Manuela Neumann, Thomas Arzberger, Safa Al-Sarraj, Istvan Bodi, Nenad Bogdanovic, Orso Bugiani, Isidro Ferrer, Ellen Gelpi, Stephen Gentleman, Giorgio Giaccone, Manuel B. Graeber, Tibor Hortobagyi, Paul G. Ince, James W. Ironside, Nikolaos Kavantzas, Andrew King, Penelope Korkolopoulou, Gábor G. Kovács, David Meyronet, Camelia Monoranu, Tatjana Nilsson, Piero Parchi, Efstratios Patsouris, Tamas Revesz, Wolfgang Roggendorf, Annemieke Rozemuller, Danielle Seilhean, Nathalie Streichenberger, Dietmar R. Thal, Stephen B. Wharton, Hans Kretzschmar

Published in: Journal of Neural Transmission | Issue 7/2015

Abstract

The BrainNet Europe consortium assessed the reproducibility in the assignment of the type of frontotemporal lobar degeneration (FTLD) with TAR DNA-binding protein (TDP) 43 following current recommendations. The agreement rates were influenced by the immunohistochemical (IHC) method and by the classification strategy followed. p62-IHC staining yielded good uniform quality of stains, but the most reliable results were obtained implementing specific Abs directed against the hallmark protein TDP43. Both assessment of the type and the extent of lesions were influenced by the Abs and by the quality of stain. Assessment of the extent of the lesions yielded poor results repeatedly; thus, the extent of pathology should not be used in diagnostic consensus criteria. Whilst 31 neuropathologists typed 30 FTLD-TDP cases, inter-rater agreement ranged from 19 to 100 per cent, being highest when applying phosphorylated TDP43/IHC. The agreement was highest when designating Type C or Type A/B. In contrast, there was a poor agreement when attempting to separate Type A or Type B FTLD-TDP. In conclusion, we can expect that neuropathologist, independent of his/her familiarity with FTLD-TDP pathology, can identify a TDP43-positive FTLD case. The goal should be to state a Type (A, B, C, D) or a mixture of Types (A/B, A/C or B/C). Neuropathologists, other clinicians and researchers should be aware of the pitfalls whilst doing so. Agreement can be reached in an inter-laboratory setting regarding Type C cases with thick and long neurites, whereas the differentiation between Types A and B may be more troublesome.

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Title: Neuropathological assessments of the pathology in frontotemporal lobar degeneration with TDP43-positive inclusions: an inter-laboratory study by the BrainNet Europe consortium
Authors: Irina Alafuzoff
Maria Pikkarainen
Manuela Neumann
Thomas Arzberger
Safa Al-Sarraj
Istvan Bodi
Nenad Bogdanovic
Orso Bugiani
Isidro Ferrer
Ellen Gelpi
Stephen Gentleman
Giorgio Giaccone
Manuel B. Graeber
Tibor Hortobagyi
Paul G. Ince
James W. Ironside
Nikolaos Kavantzas
Andrew King
Penelope Korkolopoulou
Gábor G. Kovács
David Meyronet
Camelia Monoranu
Tatjana Nilsson
Piero Parchi
Efstratios Patsouris
Tamas Revesz
Wolfgang Roggendorf
Annemieke Rozemuller
Danielle Seilhean
Nathalie Streichenberger
Dietmar R. Thal
Stephen B. Wharton
Hans Kretzschmar
Publication date: 01-07-2015
Publisher: Springer Vienna
Published in: Journal of Neural Transmission / Issue 7/2015
Print ISSN: 0300-9564
Electronic ISSN: 1435-1463
DOI: https://doi.org/10.1007/s00702-014-1304-1

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Neuropathological assessments of the pathology in frontotemporal lobar degeneration with TDP43-positive inclusions: an inter-laboratory study by the BrainNet Europe consortium

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Erratum to: Neuropathological assessments of the pathology in frontotemporal lobar degeneration with TDP43-positive inclusions: an inter-laboratory study by the BrainNet Europe consortium