a-Synuclein in filamentous inclusions of Lewy bodies from Parkinson's disease and dementia with Lewy bodies (ubiquitinysarkosyl-insoluble filamentsyimmunoelectron microscopy)

Lewy bodies and Lewy neurites are the de- fining neuropathological characteristics of Parkinson's dis- ease and dementia with Lewy bodies. They are made of abnormal filamentous assemblies of unknown composition. We show here that Lewy bodies and Lewy neurites from Parkinson's disease and dementia with Lewy bodies are stained strongly by antibodies directed against amino- terminal and carboxyl-terminal sequences of a-synuclein, showing the presence of full-length or close to full-length a-synuclein. The number of a-synuclein-stained structures exceeded that immunoreactive for ubiquitin, which is cur- rently the most sensitive marker of Lewy bodies and Lewy neurites. Staining for a-synuclein thus will replace staining for ubiquitin as the preferred method for detecting Lewy bodies and Lewy neurites. We have isolated Lewy body fila- ments by a method used for the extraction of paired helical filaments from Alzheimer's disease brain. By immunoelectron microscopy, extracted filaments were labeled strongly by anti-a-synuclein antibodies. The morphologies of the 5- to 10-nm filaments and their staining characteristics suggest that extended a-synuclein molecules run parallel to the fila- ment axis and that the filaments are polar structures. These findings indicate that a-synuclein forms the major filamen- tous component of Lewy bodies and Lewy neurites.