Neuropathology of Lewy body disease: Clinicopathological crosstalk between typical and atypical cases

Abstract

Lewy body disease (LBD) is characterized by the presence of Lewy bodies (LBs) and Lewy neurites and comprises a diagnostic spectrum that includes Parkinson's disease (PD), PD with dementia, and dementia with LBs. LBs and Lewy neurites are insoluble aggregates composed mainly of phosphorylated α-synuclein and can be widely distributed throughout the central and peripheral nervous systems. The distribution of LBs may determine the LBD phenotype. Braak hypothesized that Lewy pathology progresses ascendingly from the peripheral nervous system to the olfactory bulbs and brainstem and then to other brain regions. Braak's PD staging suggests that LBD is a prion-like disease. Most typical PD cases fit with Braak's PD staging, but the scheme fails in some cases. Alzheimer's disease, progressive supranuclear palsy, corticobasal syndrome, multiple system atrophy, frontotemporal lobar degeneration, Creutzfeldt–Jakob disease, cerebrovascular diseases, and essential tremor are common misdiagnoses for pathologically confirmed LBD. LBD exhibits considerable heterogeneity in both clinical and pathological settings, which makes clinical diagnosis challenging.