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.