Distinctive neuropathology revealed by alpha-synuclein antibodies in hereditary parkinsonism and dementia linked to chromosome 4p.

Abstract

The identification of the alpha-synuclein gene on chromosome 4q as a locus for familial Lewy-body parkinsonism and of alpha-synuclein as a component of Lewy bodies has heralded a new era in the study of Parkinson's disease. We have identified a large family with Lewy body parkinsonism linked to a novel locus on chromosome 4p15 that does not have a mutation in the alpha-synuclein gene. Here we report the clinical and neuropathological findings in an individual from this family and describe unusual high molecular weight alpha-synuclein-immunoreactive proteins in brain homogenates from brain regions with the most marked neuropathology. Distinctive histopathology was revealed with alpha-synuclein immunostaining, including pleomorphic Lewy bodies, synuclein-positive glial inclusions and widespread, severe neuritic dystrophy. We also discuss the relationship of this familial disorder to a Lewy body disease clinical spectrum, ranging from Parkinson's disease to dementia with psychosis.

• Authors: K Gwinn-Hardy, N D Mehta, M Farrer, D Maraganore, M Muenter, S H Yen, J Hardy, D W Dickson
• Journal: Acta neuropathologica (Acta Neuropathol) Vol. 99 Issue 6 Pg. 663-72 (Jun 2000) ISSN: 0001-6322 [Print] Germany
• PMID: 10867800 (Publication Type: Case Reports, Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Nerve Tissue Proteins
• SNCA protein, human
• Synucleins
• alpha-Synuclein

Topics

• Brain (pathology)
• Chromosomes, Human, Pair 4 (genetics)
• Genetic Linkage (genetics)
• Humans
• Lewy Bodies (genetics, metabolism, pathology)
• Lewy Body Disease (genetics, pathology)
• Male
• Middle Aged
• Nerve Tissue Proteins (genetics, metabolism)
• Neurons (pathology)
• Synucleins
• alpha-Synuclein