The precursor of the non-Abeta component of Alzheimer's disease amyloid (NACP) 
(also known as alpha-synuclein) is a presynaptic terminal molecule that 
abnormally accumulates in the plaques of Alzheimer's disease (AD) and in the 
Lewy bodies (LBs) of Lewy body variant of AD, diffuse Lewy body disease, and 
Parkinson's disease. To better understand the distribution of 
NACP/alpha-synuclein and its fragments in the LB-bearing neurons and neurites, 
as well as to clarify the patterns of NACP/alpha-synuclein compartmentalization, 
we studied NACP/alpha-synuclein immunoreactivity using antibodies against the 
C-terminal, N-terminal, and NAC regions after Proteinase K and formic acid 
treatment in the cortex of patients with LBs. Furthermore, studies of the 
subcellular localization of NACP/alpha-synuclein within LB-bearing neurons were 
performed by immunogold electron microscopy. These studies showed that the 
N-terminal antibody immunolabeled the LBs and dystrophic neurites with great 
intensity and, to a lesser extent, the synapses. In contrast, the C-terminal 
antibody strongly labeled the synapses and, to a lesser extent, the LBs and 
dystrophic neurites. Whereas Proteinase K treatment enhanced 
NACP/alpha-synuclein immunoreactivity with the C-terminal antibody, it 
diminished the N-terminal NACP/alpha-synuclein immunoreactivity. Furthermore, 
formic acid enhanced LB and dystrophic neurite labeling with both the C- and 
N-terminal antibodies. In addition, whereas without pretreatment only slight 
anti-NAC immunoreactivity was found in the LBs, formic acid pretreatment 
revealed an extensive anti-NAC immunostaining of LBs, plaques, and glial cells. 
Ultrastructural analysis revealed that NACP/alpha-synuclein immunoreactivity was 
diffusely distributed within the amorphous electrodense material in the LBs and 
as small clusters in the filaments of LBs and neurites. These results support 
the view that aggregated NACP/alpha-synuclein might play an important role in 
the pathogenesis of disorders associated with LBs.