alpha-Synuclein is a presynaptic terminal
protein that accumulates abnormally in plaques in
Alzheimer's disease (AD), in Lewy bodies in
Lewy body disease (LBD) and in filamentous inclusions in
multiple system atrophy. Since it has been previously shown that
proteinase K or
formic acid pretreatment enhances
alpha-synuclein immunoreactivity in Lewy bodies and plaques, we hypothesized that the immunoreactivity in tangles, glial cells and Pick bodies might be revealed by such pretreatment. Brain sections from patients with AD, LBD,
progressive supranuclear palsy (PSP),
corticobasal degeneration (CBD) and
Pick's disease were pretreated with
proteinase K or
formic acid and immunostained with
antibodies against the N-terminal, C-terminal or non-
amyloid beta component of AD
amyloid (NAC) regions of
alpha-synuclein. This study showed that after
proteinase K (but not
formic acid) pretreatment the anti-C terminus antibody immunostained neurofibrillary tangles of AD, PSP and CBD, and glial inclusions of PSP and CBD, as well as Pick bodies. Western blot analysis confirmed that in cases other than LBD, the anti-C terminus
antibodies also recognized the native
alpha-synuclein band and no cross-reactive bands were observed. In contrast, in LBD, after
formic acid pretreatment with the anti-NAC antibody astroglial cells and granular neurons were immunostained. The N-terminal region antibody only recognized the lesions in LBD cases and not those of other
neurodegenerative disorders. These results support the view that different fragments of
alpha-synuclein might play an important role in the pathogenesis of several
neurodegenerative disorders.