Numerous and widespread alpha-synuclein-negative Lewy bodies in an asymptomatic patient

Lewy bodies (LB) and pale bodies (PB), their putative precursors, can be found in a spectrum of diseases characterized by parkinsonism and/or dementia. Furthermore, LB are occasionally observed in some other neurodegenerative diseases and in normal aging. Classical LB are typically found in the brain stem, especially in the substantia nigra, where these inclusions are associated with neuronal loss and clinical signs of idiopathic Parkinson's disease (PD). The so-called cortical LB occur in the cerebral cortex, amygdala and claustrum with little or no neuronal loss and are clinically associated with dementia in dementia with LB (DLB). We describe a patient without apparent clinical signs of parkinsonism and/or dementia, whose brain contained numerous classical-like LB, pale inclusions with features of PB and transitions between these two. These inclusions had similar immunohistological (ubiquitin positive; neurofilament positive; tau negative) and ultrastructural features as the LB in PD and DLB except for the lack of immunoreactivity for alpha-synuclein. The pons and cerebral cortex showed the highest number of LB, up to 165/1.76 mm2. These numbers were contrasted by the lack of obvious neuronal loss or gliosis. The absence of alpha-synuclein reactivity in the LB in this symptomless patient corroborates the hypothesis that alpha-synuclein accumulation in LB is an important step in neurodegeneration in PD and DLB, but tones down the role of alpha-synuclein in LB formation in general. This patient seems to represent a new variant in the spectrum of diseases associated with LB.