Alpha-synuclein in familial Alzheimer disease: epitope mapping parallels dementia with Lewy bodies and Parkinson disease.

Abstract

BACKGROUND:

Alpha-synuclein is a major component of Lewy bodies (LBs) in Parkinson disease and dementia with LBs and of glial cytoplasmic inclusions in multiple system atrophy. However, epitope mapping for alpha-synuclein is distinctive in different neurodegenerative diseases. The reasons for this are poorly understood but may reflect fundamental differences in disease mechanisms.

OBJECTIVE:

To investigate the alpha-synuclein epitope mapping properties of LBs in familial Alzheimer disease.

DESIGN AND SETTING:

We compared LBs in familial Alzheimer disease with those in synucleinopathies by probing 6 brains of persons with familial Alzheimer disease using a panel of antibodies to epitopes spanning the alpha-synuclein protein. Results were compared with data from brains of persons with Parkinson disease, dementia with LBs, and multiple system atrophy.

RESULTS:

The brains of persons with familial Alzheimer disease showed consistent staining of LBs with all antibodies, similar to Parkinson disease and dementia with LBs but different from alpha-synuclein aggregates that occurred in multiple system atrophy.

CONCLUSIONS:

These data suggest that the epitope profiles of alpha-synuclein in LBs are similar, regardless of whether the biological trigger is related to synuclein or a different genetic pathway. These findings support the hypothesis that the mechanism of alpha-synuclein aggregation is the same within cell types but distinctive between cell types.

• Authors: C F Lippa, M L Schmidt, V M Lee, J Q Trojanowski
• Journal: Archives of neurology (Arch Neurol) Vol. 58 Issue 11 Pg. 1817-20 (Nov 2001) ISSN: 0003-9942 [Print] United States
• PMID: 11708989 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

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

Topics

• Aged
• Alzheimer Disease (genetics, metabolism, pathology)
• Antibodies, Monoclonal (metabolism)
• Epitope Mapping
• Female
• Humans
• Immunohistochemistry
• Lewy Bodies (chemistry)
• Lewy Body Disease (pathology)
• Male
• Middle Aged
• Nerve Tissue Proteins (analysis, chemistry, genetics, immunology)
• Neurons (metabolism, pathology)
• Parkinson Disease (pathology)
• Synucleins
• alpha-Synuclein