Staging of sporadic Parkinson disease-related alpha-synuclein pathology: inter- and intra-rater reliability

J Neuropathol Exp Neurol. 2005 Jul;64(7):623-8. doi: 10.1097/01.jnen.0000171652.40083.15.

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Female
  • Humans
  • Inclusion Bodies / metabolism
  • Inclusion Bodies / pathology
  • Male
  • Nerve Tissue Proteins / metabolism*
  • Observer Variation
  • Parkinson Disease / epidemiology*
  • Parkinson Disease / metabolism*
  • Parkinson Disease / pathology
  • Pathology, Clinical / standards*
  • Reproducibility of Results
  • Synucleins
  • alpha-Synuclein

Substances

  • Nerve Tissue Proteins
  • SNCA protein, human
  • Synucleins
  • alpha-Synuclein