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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.

Staging of Sporadic Parkinson Disease-Related α-Synuclein Pathology: Inter- and Intra-Rater Reliability