Objective To investigate the pathological features of Lewy body disease. Methods An autopsy case of an 80 year old Chinese woman suffering from Lewy body disease was studied The patient had progressive dementia and myotonia for three years and was suspected with Alzheimer dementia clinically Brain tissue was analyzed neuropathologically by using HE staining and specific staining for nervous system, immunohistochemical staining for ubiquitin and by using ? synuclein and electronic microscopy. Results Neuropathological examination revealed the most characteristic features as follows: (1) The number of melanin pigmented neurons were markedly decreased in the substantia nigra and locus ceruleus, and some typical brain stem type Lewy bodies in the residual neurons with moderate gliosis were found (2) There appeared numerous cortical type Lewy bodies in deep layers of the cerebral cortex particularly in the cingulate gyrus, hippocampus, parahippocampal gyrus, transentorhinal contex, amygdala and insula (3) There were selective spongiform changes and many Lewy related neurites in positive ubiquitin immunohistochemical staining on the CA2/3 sectors, parahippocampal gyrus and transentorhinal cortex (4) A strong positive ? synuclein immunoreactivity was found in all Lewy bodies and Lewy related neurites (5) Alzheimer disease related changes such as senile plaques and neurofibrillary tangles were scarcely found only in hippocampus and parahippocampal gyrus. Conclusion Lewy body disease is a new group of degenerative disease of the central nervous system ? synuclein may play an important role in the degeneration of neurons and their neurites may be a major component of Lewy bodies in Lewy body disease It is considered that the present case should be a pure type of diffuse Lewy body disease

OBJECTIVETo understand the possible pathogenesis of sporadic multiple system atrophy (MSA).

METHODSThe immunoreactivity and ultrastructural features of glial cytoplasmic inclusions (GCIs) in 12 autopsy patients with MSA and 4 normal control groups were studied. All regional sections from each subject were evaluated with HE staining, Klüver-Barrera (KB), Holzer's, modified Gallyas-Braak's (GB) methods and immunohistochemical staining with alpha-synuclein and ubiquitin antibodies. Pontine white matter with abundant GCIs from case 1 was examined, using conventional electron microscopy, Gallyas-Braak's electron microscopy and immunoelectron microscopy.

RESULTSThe presence of GCIs as constantly demonstrated in all MSA patients. Strong alpha-synuclein immunoreactivity was observed in all of the ubiquitinated GCIs. However, the density of alpha-synuclein positive GCIs differed from case to case, and there was no relationship between the density of GCIs and age, sex, or MSA subtype. Ultrastructural features indicated that argyrophilic granule-associated filaments of about 25 nm in diameter were the predominant constituents of GCIs, and the anti alpha-synuclein antibody selectively labeled in these filaments. No GCIs and alpha-synuclein immunoreaction were found in control brain tissues.

CONCLUSIONSGCI was a pathognomonic change in sporadic MSA patients. Accumulation of alpha-synuclein in GCIs may occur during the early stags of MSA. Seletcive alpha-synuclein positive abnormal microtubules in GCIs therefore play an important role in the pathogenesis of MSA.

Aged ; Aged, 80 and over ; Female ; Humans ; Immunohistochemistry ; Inclusion Bodies ; ultrastructure ; Male ; Microscopy, Immunoelectron ; Middle Aged ; Multiple System Atrophy ; etiology ; metabolism ; pathology ; Nerve Tissue Proteins ; analysis ; Neuroglia ; ultrastructure ; Synucleins ; alpha-Synuclein