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

• Published in: Acta neuropathologica 2000-04, Vol.99 (4), p.352-357
• Main Authors: GOMEZ-TORTOSA, E, NEWELL, K, IRIZARRY, M. C, SANDERS, J. L, HYMAN, B. T
• Format: Article
• Language: English
• Subjects: Aged; Aged, 80 and over; alpha-Synuclein; Axons; Biological and medical sciences; Brain - pathology; Cortex (entorhinal); Cortex (frontal); Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Dementia; Dementia disorders; Female; Fluorescent Antibody Technique; Hippocampus; Humans; Immunoreactivity; Investigative techniques, diagnostic techniques (general aspects); Lewy bodies; Lewy Bodies - pathology; Lewy Body Disease - pathology; Limbic System - pathology; Male; Medical sciences; Middle Aged; Neocortex; Neocortex - pathology; Nerve Tissue Proteins - analysis; Nervous system; Neurites - pathology; Neurology; Neurons - pathology; Occipital lobe; Parkinson's disease; Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques; Substantia nigra; Substantia Nigra - pathology; Synuclein; Synucleins; Ubiquitin; Ubiquitins - analysis
• ISSN: 0001-6322; 1432-0533
• 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.