Incidental Lewy body disease and preclinical Parkinson disease

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 nigro-striatal 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.