Faculty Collaboration Database

Abundant neuritic inclusions and microvacuolar changes in a case of diffuse Lewy body disease with the A53T mutation in the alpha-synuclein gene. Acta Neuropathol 2005 Sep;110(3):298-305

Date

06/28/2005

Pubmed ID

15981014

DOI

10.1007/s00401-005-1042-4

Scopus ID

2-s2.0-26444445118 (requires institutional sign-in at Scopus site)   55 Citations

Abstract

We report here a case of diffuse Lewy body disease with the A53T mutation in the alpha-synuclein gene. The proband presented at the age of 41 years with parkinsonism that was poorly responsive to levodopa. She subsequently developed cognitive impairment and moderate dementia, and died at the age of 50. Her father, paternal grandfather and uncle were all reported to have suffered from Parkinson's disease. Staining of tissue sections from the proband's brain with hematoxylin-eosin and alpha-synuclein antibodies showed small numbers of Lewy bodies in a few brain regions. This contrasted with large numbers of Lewy neurites and neuroaxonal spheroids in many brain regions. By electron microscopy, Lewy neurites consisted of abnormal filaments and dense granular material. Isolated filaments resembled those previously described in idiopathic Parkinson's disease and dementia with Lewy bodies. They were decorated by antibodies specific for the N and C termini of alpha-synuclein, indicating the presence of the full-length protein. Nucleus accumbens and the lower layers in limbic areas of the cerebral cortex showed prominent vacuolation, with frequent clustering of microvacuoles around Lewy neurites. Nerve cell loss was most extensive in dorsal motor nucleus of the vagus nerve, substantia nigra and nucleus basalis of Meynert. Neurofibrillary tangles and senile plaques were not observed. However, in several brain regions, a few widely scattered tau-positive nerve cell bodies and neurites were present. By electron microscopy, Alzheimer-type paired helical and straight filaments were seen.

Author List

Yamaguchi K, Cochran EJ, Murrell JR, Polymeropoulos MH, Shannon KM, Crowther RA, Goedert M, Ghetti B

Author

Elizabeth J. Cochran MD Adjunct Professor in the Pathology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adult
Brain
Cytoplasm
DNA Mutational Analysis
Female
Genetic Markers
Genetic Predisposition to Disease
Humans
Inclusion Bodies
Inheritance Patterns
Lewy Bodies
Lewy Body Disease
Male
Microscopy, Electron, Transmission
Mutation
Neurites
Retrospective Studies
Vacuoles
alpha-Synuclein