Incidental Lewy Body Disease and Preclinical Parkinson Disease

Abstract

BACKGROUND: The significance of Lewy bodies detected at autopsy in the brains of clinically normal individuals is uncertain but may represent preclinical Parkinson disease (PD). OBJECTIVE: To determine whether diminished striatal dopaminergic innervation and nigral cell loss are present in incidental Lewy body disease (iLBD), as one might expect if it is a forerunner of PD. DESIGN: Case-control study. SETTING: Medical records and archival brain tissue were obtained from a tertiary medical center for further study. PARTICIPANTS: Brains from clinically healthy individuals older than 60 years with alpha-synuclein-immunoreactive Lewy bodies (iLBD; n = 12) were compared with those from clinically healthy individuals with no alpha-synuclein pathologic findings (n = 31) and patients with PD (n = 25). MAIN OUTCOME MEASURES: Striatal dopaminergic integrity assessed in sections of putamen by immunofluorescence for tyrosine hydroxylase (TH) and vesicular monoamine transporter 2 (VMAT2), neuronal loss score in the substantia nigra, and distribution of Lewy bodies according to PD stage. RESULTS: Among the participants with iLBD, decreased striatal dopaminergic immunoreactivity was documented for both TH (33%) and VMAT2 (42%), compared with the pathologically normal subjects; as expected, the reductions were even greater in PD (73% decrease for TH and 96% decrease for VMAT2). Substantia nigra neuronal loss inversely correlated with both striatal TH (r = -0.84) and VMAT2 (r = -0.77). In addition, PD stage inversely correlated with both striatal VMAT2 (r = -0.85) and TH (r = -0.85). CONCLUSIONS: The results indicate that iLBD has nigrostriatal pathological features that are intermediate between those in pathologically normal persons and those with PD. The findings suggest that iLBD probably represents presymptomatic PD, rather than nonspecific, age-related alpha-synuclein pathological changes.