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

Lewy bodies (LB) and pale bodies (PB), their putative precursors, can be fo und 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 brai n stem, especially in the substantia nigra, where these inclusions are asso ciated with neuronal loss and clinical signs of idiopathic Parkinson's dise ase (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 app arent clinical signs of parkinsonism and/or dementia, whose brain contained numerous classical-like LB, pale inclusions with features of PB and transi tions between these two. These inclusions had similar immunohistological (u biquitin positive; neurofilament positive; tau negative) and ultrastructura l features as the LB in PD and DLB except for the lack of immunoreactivity for alpha-synuclein. The pens and cerebral cortex showed the highest number of LB, up to 165/1.76 mm(2). 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 alp ha-synuclein accumulation in LB is an important step in neurodegeneration i n 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.