Lewy Bodies in Progressive Supranuclear Palsy Represent an Independent Disease Process

Abstract

Progressive supranuclear palsy (PSP) is a neurodegenerative tauopathy characterized by Parkinsonism, vertical gaze palsy, and early falls. Lewy bodies (LBs) are detected in approximately 10% of PSP cases, but there is little information on the relationship of LBs to tau pathology. We determined the frequency of LBs in a large series of autopsy-confirmed cases of PSP and studied the density and distribution of LBs, including Parkinson disease stage, in cases with LBs (PSP/LBD). PSP/LBD was compared with pure LB disease (LBD), including assessment of neuronal loss in key brainstem nuclei. Immunohistochemistry for alpha-synuclein revealed LBs in 31 of 290 PSP cases (11%). One case had multiple system atrophy in addition to PSP and was excluded from further study along with 2 PSP/LBD cases with concurrent Alzheimer disease. The 29 cases of PSP/LBD were compared with 30 cases of PSP and 24 cases of LBD. The age, sex, brain weight, Braak neurofibrillary tangle (NFT) stage, as well as counts of NFTs and senile plaques were not different among PSP, LBD, and PSP/LBD, but disease duration was longer in LBD. The Parkinson disease stage was similar, but the density of LBs in most subcortical nuclei tended to be greater in LBD than in PSP/LBD. In contrast, substantia nigra neuronal loss was greater in PSP/LBD than both PSP and LBD. Double immunostaining demonstrated alpha-synuclein and tau in different neurons with few exceptions. The findings suggest that LBs in PSP are similar in distribution to those in LBD and independent of tau pathology. The greater density of LBs in LBD compared with PSP/LBD may be the result of longer disease duration in LBD, whereas greater neuronal loss in the substantia nigra in PSP/LBD may be the result of vulnerability of this brain region to both disease processes.