Journal
ACTA NEUROPATHOLOGICA
Volume 99, Issue 4, Pages 352-357Publisher
SPRINGER VERLAG
DOI: 10.1007/s004010051135
Keywords
Lewy bodies; alpha-synuclein; ubiquitin; dementia; Parkinson's disease
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Funding
- NIA NIH HHS [P5O-AGO5134, AGO8487] Funding Source: Medline
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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.
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