title: Staging of sporadic Parkinson disease-related alpha-synuclein pathology: inter- and intra-rater reliability.
abstract: Sporadic Parkinson disease (sPD) is characterized by alpha-synuclein (alpha-syn) inclusions. The distribution of such inclusions appears to relate to disease progression and severity. We propose and test a simple staging protocol based on the presence of alpha-syn immunoreactivity in 5 paraffin sections that, taken together, contain up to 8 vulnerable brain regions. Six stages of alpha-syn pathology reminiscent for sPD are defined based on the presence or absence of inclusions in the assessed sections. Six observers from 5 different institutions rated 21 cases on the basis of written instructions only. The agreement of the raters was highly significant with a mean error below one stage. Both inter- and intra-rater reliability were also substantial to almost perfect as analyzed by paired comparison between all raters. We propose that the staging procedure for alpha-syn pathology is suitable for application in routine neuropathology and brain banking. Clearly defined stages of alpha-synpathology might aid the comparability between studies and also help to distinguish sPD from other synucleinopathies.
authors.affiliation: Institute for Clinical Neuroanatomy, J. W. Goethe University Clinic, Frankfurt/M., Germany. ch.mueller@med.uni-frankfurt.de
authors.forename: Christian M
authors.initials: CM
authors.lastname: Müller
authors.forename: Rob A I
authors.initials: RA
authors.lastname: de Vos
authors.forename: Claude-Alain
authors.initials: CA
authors.lastname: Maurage
authors.forename: Dietmar R
authors.initials: DR
authors.lastname: Thal
authors.forename: Markus
authors.initials: M
authors.lastname: Tolnay
authors.forename: Heiko
authors.initials: H
authors.lastname: Braak
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D006801:Humans; D002479:Inclusion Bodies / Q000378:metabolism / Q000473:pathology; D008297:Male; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D015588:Observer Variation; D010300:Parkinson Disease / Q000453:epidemiology* / Q000378:metabolism* / Q000473:pathology; D010338:Pathology, Clinical / Q000592:standards*; D015203:Reproducibility of Results; D051843:Synucleins; D051844:alpha-Synuclein
chemical_list: D009419:Nerve Tissue Proteins; C497604:SNCA protein, human; D051843:Synucleins; D051844:alpha-Synuclein