title: alpha-Synuclein immunoreactivity in dementia with Lewy bodies: morphological staging and comparison with ubiquitin immunostaining.
abstract: 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.
authors.affiliation: Neurology Department, Massachusetts General Hospital, Charlestown 02129, USA.
authors.forename: E
authors.initials: E
authors.lastname: Gómez-Tortosa
authors.forename: K
authors.initials: K
authors.lastname: Newell
authors.forename: M C
authors.initials: MC
authors.lastname: Irizarry
authors.forename: J L
authors.initials: JL
authors.lastname: Sanders
authors.forename: B T
authors.initials: BT
authors.lastname: Hyman
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001921:Brain / Q000473:pathology*; D005260:Female; D005455:Fluorescent Antibody Technique; D006801:Humans; D016631:Lewy Bodies / Q000473:pathology; D020961:Lewy Body Disease / Q000473:pathology*; D008032:Limbic System / Q000473:pathology; D008297:Male; D008875:Middle Aged; D019579:Neocortex / Q000473:pathology; D009419:Nerve Tissue Proteins / Q000032:analysis*; D016501:Neurites / Q000473:pathology; D009474:Neurons / Q000473:pathology*; D013378:Substantia Nigra / Q000473:pathology; D051843:Synucleins; D014452:Ubiquitins / Q000032:analysis*; D051844:alpha-Synuclein
chemical_list: D009419:Nerve Tissue Proteins; C497604:SNCA protein, human; D051843:Synucleins; D014452:Ubiquitins; D051844:alpha-Synuclein