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

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 immunoreactivi ty 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 a nd ubiquitin immunostaining in 25 cases meeting neuropathological criteria for DLB. alpha-Synuclein immunostaining was more specific than ubiquitin im munostaining in that it differentiated LB from globose tangles. It was also slightly more sensitive, staining 4-5% more intracytoplasmic structures, e specially diffuse alpha-synuclein deposits that were ubiquitin negative. In addition to LB, alpha-synuclein staining showed filiform and globose neuri tes in the substantia nigra, CA2-3 regions of the hippocampus, and entorhin al cortex. A spectrum of alpha-synuclein staining was seen in substantia ni gra: from diffuse "cloud-like" inclusions to aggregated intracytoplasmic in clusions with variable ubiquitin staining to classic LB. We hypothesize tha t these represent different stages in LB formation.