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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
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
Univ Eastern Finland, Dept Clin Med, Kuopio, Finland.
Univ Tubingen, German Ctr Neurodegenerat Dis, Dept Neuropatol, Tubingen, Germany; DZNE, Tubingen, Germany.
Univ Munich, Ctr Neuropathol & Prion Res, Munich, Germany.
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2015 (English)In: Journal of neural transmission, ISSN 0300-9564, E-ISSN 1435-1463, Vol. 122, no 7, 957-972 p.Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
2015. Vol. 122, no 7, 957-972 p.
Keyword [en]
Ubiquitin; p62; TDP43; Phosphorylated TDP43; FTLD-TDP; BrainNet Europe; Immunohistochemistry; Inter-laboratory study; Tissue
National Category
Neurosciences
Identifiers
URN: urn:nbn:se:uu:diva-239546DOI: 10.1007/s00702-014-1304-1ISI: 000358159400005PubMedID: 25239189OAI: oai:DiVA.org:uu-239546DiVA: diva2:774804
Funder
EU, European Research Council
Note

Correction in: Journal of Neural Transmission, 2014, vol. 122, issue 7, pages 973-974, DOI: 10.1007/s00702-014-1337-5

Available from: 2014-12-29 Created: 2014-12-29 Last updated: 2017-12-05Bibliographically approved

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Alafuzoff, Irina

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