title: Staging/typing of Lewy body related alpha-synuclein pathology: a study of the BrainNet Europe Consortium.
abstract: When 22 members of the BrainNet Europe (BNE) consortium assessed 31 cases with alpha-synuclein (alphaS) immunoreactive (IR) pathology applying the consensus protocol described by McKeith and colleagues in 2005, the inter-observer agreement was 80%, being lowest in the limbic category (73%). When applying the staging protocol described by Braak and colleagues in 2003, agreement was only 65%, and in some cases as low as 36%. When modifications of these strategies, i.e., McKeith's protocol by Leverenz and colleagues from 2009, Braak's staging by Müller and colleagues from 2005 were applied then the agreement increased to 78 and 82%, respectively. In both of these modifications, a reduced number of anatomical regions/blocks are assessed and still in a substantial number of cases, the inter-observer agreement differed significantly. Over 80% agreement in both typing and staging of alphaS pathology could be achieved when applying a new protocol, jointly designed by the BNE consortium. The BNE-protocol assessing alphaS-IR lesions in nine blocks offered advantages over the previous modified protocols because the agreement between the 22 observers was over 80% in most cases. Furthermore, in the BNE-protocol, the alphaS pathology is assessed as being present or absent and thus the quality of staining and the assessment of the severity of alphaS-IR pathology do not alter the inter-observer agreement, contrary to other assessment strategies. To reach these high agreement rates an entity of amygdala-predominant category was incorporated. In conclusion, here we report a protocol for assessing alphaS pathology that can achieve a high inter-observer agreement for both the assignment to brainstem, limbic, neocortical and amygdala-predominant categories of synucleinopathy and the Braak stages.
authors.affiliation: Department of Neuroscience and Neurology, Kuopio University, Kuopio, Finland. Irina.Alafuzoff@genpat.uu.se
authors.forename: Irina
authors.initials: I
authors.lastname: Alafuzoff
authors.forename: Paul G
authors.initials: PG
authors.lastname: Ince
authors.forename: Thomas
authors.initials: T
authors.lastname: Arzberger
authors.forename: Safa
authors.initials: S
authors.lastname: Al-Sarraj
authors.forename: Jeanne
authors.initials: J
authors.lastname: Bell
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: 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: Piero
authors.initials: P
authors.lastname: Parchi
authors.forename: Laura
authors.initials: L
authors.lastname: Parkkinen
authors.forename: Efstratios
authors.initials: E
authors.lastname: Patsouris
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Roggendorf
authors.forename: Annemieke
authors.initials: A
authors.lastname: Rozemuller
authors.forename: Christine
authors.initials: C
authors.lastname: Stadelmann-Nessler
authors.forename: Nathalie
authors.initials: N
authors.lastname: Streichenberger
authors.forename: Dietmar R
authors.initials: DR
authors.lastname: Thal
authors.forename: Hans
authors.initials: H
authors.lastname: Kretzschmar