A number of neurodegenerative diseases including Parkinson's disease, dementia 
with Lewy bodies (DLB) and multiple system atrophy are characterized by the 
formation and intraneuronal accumulation of fibrillar aggregates of 
alpha-synuclein (alpha-syn) protein in affected brain regions. These and other 
findings suggest that the accumulation of alpha-syn in the brain plays an 
important role in the pathogenesis of these diseases. However, more recently it 
has been reported that early amyloid aggregates or 'soluble oligomers' are the 
pathogenic species that lead to neurodegeneration and neuronal cell death rather 
than the later 'mature fibrils'. In this study, we investigated the presence of 
alpha-syn oligomers in brain lysates prepared from frozen post-mortem brains of 
normal, Alzheimer's disease and DLB patients. The brain extracts were subjected 
to high speed centrifugation, to remove insoluble alpha-syn aggregates, followed 
by specific detection of soluble oligomers in the supernatants by employing 
FILA-1, an antibody that specifically binds to alpha-syn aggregates, but not to 
alpha-syn monomers, or to tau or beta-amyloid aggregates. Using this novel 
enzyme-linked immunosorbent assay (ELISA) method to quantify the amounts of 
alpha-syn oligomers in the brain extracts, our data clearly show an increase in 
the levels of soluble oligomers of alpha-syn in the DLB brains compared to those 
with Alzheimer's disease and the controls (P < 0.0001). Our findings provide 
strong evidence to support the contention that elevated soluble oligomers of 
alpha-syn are involved in the pathogenesis of DLB. Furthermore, these findings 
establish FILA-1 as a very sensitive tool for the detection of oligomeric forms 
of alpha-syn in human brain lysates.