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Original Contribution
August 2008

Incidental Lewy Body Disease and Preclinical Parkinson Disease

Author Affiliations

Author Affiliations: Departments of Neuroscience (Drs DelleDonne, Fujishiro, and Dickson and Mr Ahmed) and Neurology (Drs Wszolek and Uitti), Mayo Clinic, Jacksonville, Florida; Neurological Associates of Tulsa, Tulsa, Oklahoma (Dr Klos); and Departments of Laboratory Medicine and Pathology (Dr Parisi) and Neurology (Drs Josephs, Frigerio, Burnett, and Ahlskog), Mayo Clinic, Rochester, Minnesota. Mr Ahmed is a doctoral candidate at the Medical Research Council Centre for Neurodegeneration Research, King's College London, London, England.

Arch Neurol. 2008;65(8):1074-1080. doi:10.1001/archneur.65.8.1074
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 α-synuclein–immunoreactive Lewy bodies (iLBD; n = 12) were compared with those from clinically healthy individuals with no α-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 α-synuclein pathological changes.

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