alpha-Synuclein immunoreactivity in dementia with Lewy bodies: morphological staging and comparison with ubiquitin immunostaining

Acta Neuropathol. 2000 Apr;99(4):352-7. doi: 10.1007/s004010051135.


alpha-Synuclein is a presynaptic protein recently identified as a specific component of Lewy bodies (LB) and Lewy neurites. The aim of this study was to assess the morphology and distribution of alpha-synuclein immunoreactivity in cases of dementia with LB (DLB), and to compare alpha-synuclein with ubiquitin immunostaining. We examined substantia nigra, paralimbic regions (entorhinal cortex, cingulate gyrus, insula and hippocampus), and neocortex (frontal and occipital association cortices) with double alpha-synuclein and ubiquitin immunostaining in 25 cases meeting neuropathological criteria for DLB. alpha-Synuclein immunostaining was more specific than ubiquitin immunostaining in that it differentiated LB from globose tangles. It was also slightly more sensitive, staining 4-5% more intracytoplasmic structures, especially diffuse alpha-synuclein deposits that were ubiquitin negative. In addition to LB, alpha-synuclein staining showed filiform and globose neurites in the substantia nigra, CA2-3 regions of the hippocampus, and entorhinal cortex. A spectrum of alpha-synuclein staining was seen in substantia nigra: from diffuse "cloud-like" inclusions to aggregated intracytoplasmic inclusions with variable ubiquitin staining to classic LB. We hypothesize that these represent different stages in LB formation.

Publication types

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

MeSH terms

  • Aged
  • Aged, 80 and over
  • Brain / pathology*
  • Female
  • Fluorescent Antibody Technique
  • Humans
  • Lewy Bodies / pathology
  • Lewy Body Disease / pathology*
  • Limbic System / pathology
  • Male
  • Middle Aged
  • Neocortex / pathology
  • Nerve Tissue Proteins / analysis*
  • Neurites / pathology
  • Neurons / pathology*
  • Substantia Nigra / pathology
  • Synucleins
  • Ubiquitins / analysis*
  • alpha-Synuclein


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