Three-layered structure shared between Lewy bodies and Lewy neurites - Three-dimensional reconstruction of triple-labeled sections

Lewy bodies (LBs) and Lewy neurites (LNs) are the hallmarks of Parkinson's disease (PD). Although LBs and LNs, frequently coexistent, share some histological properties, their appearances are quite different under conventional two-dimensional observation. In order to clarify how these apparently different structures (LBs and LNs) are related during their formation, we performed three-dimensional observation on post-mortem brainstem tissues with PD. Sixty-mu m thick floating sections were multi-immunofluorolabeled for alpha-synuclein (alpha S), ubiquitin (Ub) and neurofilament (NF). Serial confocal images were reconstructed with software. External three-dimensional configuration of LBs, double-labeled for alpha S and NF, exhibited frequent continuity with LNs (70%). Internally, alpha S and Ub formed the three-dimensional concentric inner layers and NF rimmed these inner layers. This layered structure was shared among spherical LBs, rod-shaped LNs and even convoluted forms of LBs/LNs. Furthermore, each layer exhibited continuity without interruption even in the convoluted form and around its junction to spherical LBs. This three-layered structure shared among various Lewy pathologies and their layered continuity on three-dimensional basis favor the hypothesis that LNs evolve into LBs. Besides progression from pale bodies to LBs, structural evolution from LNs into LBs may provide an alternative explanation for the variability of alpha S deposits and their interrelation.