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

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. KovácsDavid 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

Research output: Contribution to journalArticle

15 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)957-972
Number of pages16
JournalJournal of Neural Transmission
Volume122
Issue number7
DOIs
Publication statusPublished - Jul 23 2015

Fingerprint

Frontotemporal Lobar Degeneration
DNA-Binding Proteins
Pathology
Coloring Agents
Neurites
Consensus
Research Personnel
Staining and Labeling
Neuropathology
Proteins

Keywords

  • BrainNet Europe
  • FTLD-TDP
  • Immunohistochemistry
  • Inter-laboratory study
  • p62
  • Phosphorylated TDP43
  • TDP43
  • Tissue microarray
  • Ubiquitin

ASJC Scopus subject areas

  • Biological Psychiatry
  • Neurology
  • Clinical Neurology
  • Psychiatry and Mental health

Cite this

Neuropathological assessments of the pathology in frontotemporal lobar degeneration with TDP43-positive inclusions : an inter-laboratory study by the BrainNet Europe consortium. / Alafuzoff, Irina; Pikkarainen, Maria; Neumann, Manuela; Arzberger, Thomas; Al-Sarraj, Safa; Bodi, Istvan; Bogdanovic, Nenad; Bugiani, Orso; Ferrer, Isidro; Gelpi, Ellen; Gentleman, Stephen; Giaccone, Giorgio; Graeber, Manuel B.; Hortobagyi, Tibor; Ince, Paul G.; Ironside, James W.; Kavantzas, Nikolaos; King, Andrew; Korkolopoulou, Penelope; Kovács, Gábor G.; Meyronet, David; Monoranu, Camelia; Nilsson, Tatjana; Parchi, Piero; Patsouris, Efstratios; Revesz, Tamas; Roggendorf, Wolfgang; Rozemuller, Annemieke; Seilhean, Danielle; Streichenberger, Nathalie; Thal, Dietmar R.; Wharton, Stephen B.; Kretzschmar, Hans.

In: Journal of Neural Transmission, Vol. 122, No. 7, 23.07.2015, p. 957-972.

Research output: Contribution to journalArticle

Alafuzoff, I, Pikkarainen, M, Neumann, M, Arzberger, T, Al-Sarraj, S, Bodi, I, Bogdanovic, N, Bugiani, O, Ferrer, I, Gelpi, E, Gentleman, S, Giaccone, G, Graeber, MB, Hortobagyi, T, Ince, PG, Ironside, JW, Kavantzas, N, King, A, Korkolopoulou, P, Kovács, GG, Meyronet, D, Monoranu, C, Nilsson, T, Parchi, P, Patsouris, E, Revesz, T, Roggendorf, W, Rozemuller, A, Seilhean, D, Streichenberger, N, Thal, DR, Wharton, SB & Kretzschmar, H 2015, 'Neuropathological assessments of the pathology in frontotemporal lobar degeneration with TDP43-positive inclusions: an inter-laboratory study by the BrainNet Europe consortium', Journal of Neural Transmission, vol. 122, no. 7, pp. 957-972. https://doi.org/10.1007/s00702-014-1304-1
Alafuzoff, Irina ; Pikkarainen, Maria ; Neumann, Manuela ; Arzberger, Thomas ; Al-Sarraj, Safa ; Bodi, Istvan ; Bogdanovic, Nenad ; Bugiani, Orso ; Ferrer, Isidro ; Gelpi, Ellen ; Gentleman, Stephen ; Giaccone, Giorgio ; Graeber, Manuel B. ; Hortobagyi, Tibor ; Ince, Paul G. ; Ironside, James W. ; Kavantzas, Nikolaos ; King, Andrew ; Korkolopoulou, Penelope ; Kovács, Gábor G. ; Meyronet, David ; Monoranu, Camelia ; Nilsson, Tatjana ; Parchi, Piero ; Patsouris, Efstratios ; Revesz, Tamas ; Roggendorf, Wolfgang ; Rozemuller, Annemieke ; Seilhean, Danielle ; Streichenberger, Nathalie ; Thal, Dietmar R. ; Wharton, Stephen B. ; Kretzschmar, Hans. / Neuropathological assessments of the pathology in frontotemporal lobar degeneration with TDP43-positive inclusions : an inter-laboratory study by the BrainNet Europe consortium. In: Journal of Neural Transmission. 2015 ; Vol. 122, No. 7. pp. 957-972.
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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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AU - Korkolopoulou, Penelope

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AU - Monoranu, Camelia

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AU - Parchi, Piero

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