ACCUMULATION OF ALPHA-SYNUCLEIN NACP IS A CYTOPATHOLOGICAL FEATURE COMMON TO LEWY BODY DISEASE AND MULTIPLE SYSTEM ATROPHY/

Recently, we have shown that the precursor of the non-A beta component of Alzheimer's disease amyloid (NACP), also known as alpha-synuclein, is a major component of Lewy bodies (LBs) as well as neuronal and gli al cytoplasmic inclusions in multiple system atrophy (MSA). Introducti on To elucidate whether the accumulation of NACP is specific to LB dis ease and MSA, we further studied 83 autopsied cases with various neuro logical disorders, using anti-NACP antibodies. In LB disease, NACP imm unoreactivity was present in all of the LBs and Lewy neurites in both the central and peripheral nervous systems, the pale bodies in the sub stantia nigra, and dystrophic neurites in the hippocampal CA2/3 region . Immunoelectron microscopy revealed that the reaction product was loc alized within filamentous structures and associated granular structure s. In MSA, NACP immunoreactivity was found in the intracytoplasmic inc lusions of both neuronal and oligodendroglial cells, neuronal intranuc lear inclusions, and swollen neuronal processes. No NACP immunoreactiv ity was found in a variety of other neuronal or glial inclusions in ot her disorders, including Alzheimer's disease, Pick's disease, progress ive supranuclear palsy, corticobasal degeneration, motor neuron diseas e and tripler-repeat diseases. These findings strongly suggest that th e accumulation of NACP is a cytopathological feature common to LB dise ase and MSA.