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 Pa rkinson disease and dementia with LBs and of glial cytoplasmic inclusions i n multiple system atrophy. However, epitope mapping for alpha-synuclein is distinctive in different neurodegenerative diseases. The reasons for this a re poorly understood but may reflect fundamental differences in disease mec hanisms, 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 thos e in synucleinopathies by probing 6 brains of persons with familial Alzheim er disease using a panel of antibodies to epitopes spanning the alpha-synuc lein protein. Results were compared with data from brains of persons with P arkinson disease, dementia with LBs, and multiple system atrophy. Results: The brains of persons with familial Alzheimer disease showed consi stent staining of LBs with all antibodies, similar to Parkinson disease and dementia with LBs but different from alpha-synuclein aggregates that occur red in multiple system atrophy. Conclusions: These data suggest that the epitope profiles of alpha-synuclei n in LBs are similar, regardless of Whether the biological trigger is relat ed to synuclein or a different genetic pathway. These findings support the hypothesis that the mechanism of alpha-synuclein aggregation is the same wi thin cell types but distinctive between cell types.