LB, Lewy body; NFT, neurofibrillary tangle °a-synuclein immunoreactive 'tau-immunoreactive
LB, Lewy body; NFT, neurofibrillary tangle °a-synuclein immunoreactive 'tau-immunoreactive neuropathologists are reluctant to make the diagnosis in their absence. Classical LBs are spherical intracytoplasmic neuronal inclusions, measuring 8-30 |im in diameter, with an eosinophilic hyaline core and a pale-staining peripheral halo (Fig. 1B). They occasionally have a more complex, multilobar shape and more than one LBs may occur in a single cell. Following neuronal death, LBs may remain as an extracellular deposit in the neuropil. Ultrastructurally they are composed of radially arranged 7-to 20-nm filaments associated with granular electron-dense material.
An additional finding in most cases of PD is the presence of pale bodies: ill-defined rounded areas of granular pale-staining eosinophilic material that also occur in pigmented neurons of the substantia nigra and locus ceruleus (Fig. 1C). Although they are distinguished from LBs histologically, their similar immunocytochemical profile suggests they likely represent precursors to LBs (18,19).
LBs are difficult to isolate and purify and so most of our understanding of their chemical composition is based on immunohistochemical studies. Until recently, the two main components were
thought to be neurofilament proteins and ubiquitin, although many other protein and non-proteina-ceous elements are also recognized (20-22). The biochemistry of LBs was clarified following the discovery of mutations in the gene for a-synuclein in some families with autosomal dominant PD (23). a-Synuclein is a presynaptic nerve terminal protein and immunohistochemistry of normal brain tissue shows punctate staining around neuronal perikarya. Direct involvement of a-synuclein in the pathogenesis of all LB disorders (sporadic as well as familial PD and dementia with LB) is supported by immunohistochemical studies confirming a-synuclein as a major component of both brainstem and cortical LB, as well as pale bodies and Lewy-related neurites (19,24). In addition to these neuronal pathologies, recent reports have described the presence of argyrophilic, a-synuclein-positive cytoplasmic inclusions in both astrocytes and oligodendrocytes in PD (Fig. 1D) (25,26). The consistency and significance of this glial pathology awaits clarification.
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