Accumulation of NACP/alpha-synuclein in Lewy body disease and multiple system atrophy

Objectives-NACP/alpha-synuclein is an aetiological gene product in familial Parkinson's disease. To clarify the pathological role of NACP/alpha-synucl ein in sporadic Parkinson's disease and other related disorders including d iffuse Lewy body disease (DLBD) and multiple system atrophy (MSA), paraffin sections were examined immunocytochemically using anti-NACP/ alpha-synucle in antibodies. Methods-A total of 58 necropsied brains, from seven patients with Parkinson 's disease, five with DLBD, six with MSA, 12 with Alzheimer's disease, one with Down's syndrome, one with amyotrophic lateral sclerosis (ALS), three w ith ALS and dementia, one with Huntington's disease, two with progressive s upranuclear palsy (PSP), one with Pick's disease, one with myotonic dystrop hy, and three with late cerebellar cortical atrophy (LCCA), and 15 elderly normal controls were examined. Results-In addition to immunoreactive Lewy bodies, widespread accumulation of NACP/alpha-synuclein was found in neurons and astrocytes from the brains tem and basal ganglia to the cerebral cortices in Parkinson's disease/DLBD. NACP/alpha-synuclein accumulates in oligodendrocytes from the spinal cord, the brain stem to the cerebellar white matter, and inferior olivary neuron s in MSA. These widespread accumulations were not seen in other types of de mentia or spinocerebellar ataxia. Conclusion-Completely different types of NACP/alpha-synuclein accumulation in Parkinson's disease/DLBD and MSA suggest that accumulation is a major st ep in the pathological cascade of both diseases and provides novel strategi es for the development of therapies.