NACP, a presynaptic protein, immunoreactivity in Lewy bodies in Parkinson's disease

NACP, originally identified as a precursor of the non-Abeta component of Alzheimer's disease amyloid (NAC), is now known to be identical to alpha-synuclein, a presynaptic protein in the human brain. Recently, a mutation in the alpha-synuclein gene in families with autosomal dominant Parkinson's disease (PD) was identified. We carried out immunohistochemical examinations of the brains of sporadic PD patients using anti-NACP and anti-ubiquitin antibodies. Consistent with previous studies, the anti-NACP antibody immunostained the neuropil in a punctate pattern throughout the brain. Moreover, much stronger NACP immunoreactivity was found in Lewy bodies and degenerating neurites in the brainstem. Serial sections immunolabeled with anti-ubiquitin or anti-NACP showed that all ubiquitin-immunoreactive LBs were also NACP-immunoreactive. These findings suggest that alteration of NACP metabolism is involved in the pathogenesis of PD, particularly in Lewy body formation, leading to neurodegeneration.