Lewy bodies and Lewy neurites are the defining neuropathological characteristics 
of Parkinson's disease 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 alpha-synuclein, showing the presence of full-length or close to 
full-length alpha-synuclein. The number of alpha-synuclein-stained structures 
exceeded that immunoreactive for ubiquitin, which is currently the most 
sensitive marker of Lewy bodies and Lewy neurites. Staining for alpha-synuclein 
thus will replace staining for ubiquitin as the preferred method for detecting 
Lewy bodies and Lewy neurites. We have isolated Lewy body filaments 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-alpha-synuclein antibodies. The morphologies of the 5- to 10-nm 
filaments and their staining characteristics suggest that extended 
alpha-synuclein molecules run parallel to the filament axis and that the 
filaments are polar structures. These findings indicate that alpha-synuclein 
forms the major filamentous component of Lewy bodies and Lewy neurites.