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


METHODS
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.
Lippa
C F
CF
Department of Neurology, Medical College of Pennsylvania--Hahnemann University, 3300 Henry Ave, Philadelphia, PA 19129, USA. carol.lippa@drexel.edu
Schmidt
M L
ML
Lee
V M
VM
Trojanowski
J Q
JQ
D000368:Aged; D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D000911:Antibodies, Monoclonal / Q000378:metabolism; D018604:Epitope Mapping; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D016631:Lewy Bodies / Q000737:chemistry*; D020961:Lewy Body Disease / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000032:analysis* / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D010300:Parkinson Disease / Q000473:pathology; D051843:Synucleins; D051844:alpha-Synuclein
D000911:Antibodies, Monoclonal; D009419:Nerve Tissue Proteins; C497604:SNCA protein, human; D051843:Synucleins; D051844:alpha-Synuclein