title: Neuropathological assessments of the pathology in frontotemporal lobar degeneration with TDP43-positive inclusions: an inter-laboratory study by the BrainNet Europe consortium.
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.
authors.affiliation: Section of Clinical Pathology Uppsala University Hospital, Rudbeck's Laboratory, Department of Immunology, Genetics and Pathology, Uppsala University, 751 85, Uppsala, Sweden, irina.alafuzoff@igp.uu.se.
authors.forename: Irina
authors.initials: I
authors.lastname: Alafuzoff
authors.forename: Maria
authors.initials: M
authors.lastname: Pikkarainen
authors.forename: Manuela
authors.initials: M
authors.lastname: Neumann
authors.forename: Thomas
authors.initials: T
authors.lastname: Arzberger
authors.forename: Safa
authors.initials: S
authors.lastname: Al-Sarraj
authors.forename: Istvan
authors.initials: I
authors.lastname: Bodi
authors.forename: Nenad
authors.initials: N
authors.lastname: Bogdanovic
authors.forename: Orso
authors.initials: O
authors.lastname: Bugiani
authors.forename: Isidro
authors.initials: I
authors.lastname: Ferrer
authors.forename: Ellen
authors.initials: E
authors.lastname: Gelpi
authors.forename: Stephen
authors.initials: S
authors.lastname: Gentleman
authors.forename: Giorgio
authors.initials: G
authors.lastname: Giaccone
authors.forename: Manuel B
authors.initials: MB
authors.lastname: Graeber
authors.forename: Tibor
authors.initials: T
authors.lastname: Hortobagyi
authors.forename: Paul G
authors.initials: PG
authors.lastname: Ince
authors.forename: James W
authors.initials: JW
authors.lastname: Ironside
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Kavantzas
authors.forename: Andrew
authors.initials: A
authors.lastname: King
authors.forename: Penelope
authors.initials: P
authors.lastname: Korkolopoulou
authors.forename: Gábor G
authors.initials: GG
authors.lastname: Kovács
authors.forename: David
authors.initials: D
authors.lastname: Meyronet
authors.forename: Camelia
authors.initials: C
authors.lastname: Monoranu
authors.forename: Tatjana
authors.initials: T
authors.lastname: Nilsson
authors.forename: Piero
authors.initials: P
authors.lastname: Parchi
authors.forename: Efstratios
authors.initials: E
authors.lastname: Patsouris
authors.forename: Tamas
authors.initials: T
authors.lastname: Revesz
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Roggendorf
authors.forename: Annemieke
authors.initials: A
authors.lastname: Rozemuller
authors.forename: Danielle
authors.initials: D
authors.lastname: Seilhean
authors.forename: Nathalie
authors.initials: N
authors.lastname: Streichenberger
authors.forename: Dietmar R
authors.initials: DR
authors.lastname: Thal
authors.forename: Stephen B
authors.initials: SB
authors.lastname: Wharton
authors.forename: Hans
authors.initials: H
authors.lastname: Kretzschmar
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005060:Europe; D005260:Female; D057174:Frontotemporal Lobar Degeneration / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D002479:Inclusion Bodies / Q000378:metabolism*; D008297:Male; D016501:Neurites / Q000473:pathology; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D010766:Phosphorylation; D012189:Retrospective Studies; D000071456:Sequestosome-1 Protein; D046888:Tissue Array Analysis; D025801:Ubiquitin / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D004268:DNA-Binding Proteins; C099718:SQSTM1 protein, human; D000071456:Sequestosome-1 Protein; C000598624:TARDBP protein, human; D025801:Ubiquitin