 |
|
 -Synuclein in Familial Alzheimer Disease
Epitope Mapping Parallels Dementia With Lewy Bodies and Parkinson Disease
Carol F. Lippa, MD;
M. Luise Schmidt, PhD;
Virginia M.-Y. Lee, PhD;
John Q. Trojanowski, MD, PhD
Arch Neurol. 2001;58:1817-1820.
Background  -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 -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 -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 -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
-synuclein aggregates that occurred in multiple system atrophy.
Conclusions These data suggest that the epitope profiles
of -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
-synuclein aggregation is the same within cell types but distinctive
between cell types.
From the Department of Neurology, Medical College
of Pennsylvania–Hahnemann University (Dr Lippa),
and the Center for Neurodegenerative Disease Research, Department
of Pathology and Laboratory Medicine, University of Pennsylvania School of
Medicine (Drs Schmidt, Lee, and Trojanowski), Philadelphia.
Corresponding author and reprints: Carol F. Lippa, MD, Department of
Neurology, Medical College of Pennsylvania–Hahnemann University, 3300
Henry Ave, Philadelphia, PA 19129 (e-mail: carol.lippa{at}drexel.edu).
RELATED ARTICLE
Archives of Neurology Reader's Choice: Continuing Medical Education
Arch Neurol. 2001;58(11):1942-1944.
FULL TEXT
THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES
Dementia with Lewy Bodies: Molecular Pathogenesis and Implications for Classification
Cummings
J Geriatr Psychiatry Neurol 2004;17:112-119.
ABSTRACT
Apolipoprotein E controls the risk and age at onset of Parkinson disease
Li et al.
Neurology 2004;62:2005-2009.
ABSTRACT
| FULL TEXT
Clinical, Pathological, and Biochemical Spectrum of Alzheimer Disease Associated With PS-1 Mutations
Lleo et al.
AJGP 2004;12:146-156.
ABSTRACT
| FULL TEXT
|
