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From the Departments of Neurology (Drs. Hurtig, Clark, Glosser, Stern, and Gollomp), Pathology and Laboratory Medicine (Center for Neurodegenerative Disease Research) (Drs. Trojanowski, Galvin, Schmidt, and Lee), Population Studies Center (Dr. Ewbank), and Department of Psychiatry (Dr. Arnold), University of Pennsylvania; and the Department of Neurology (Dr. Galvin), MCP–Hahnemann University, Philadelphia, PA.
Address correspondence and reprint requests to Dr. Howard Hurtig, 330 South Ninth Street, Philadelphia, PA 19107; e-mail: hihurtig{at}pahosp.com
BACKGROUND: Dementia is a frequent complication of idiopathic parkinsonism or PD, usually occurring later in the protracted course of the illness. The primary site of neuropathologic change in PD is the substantia nigra, but the neuropathologic and molecular basis of dementia in PD is less clear. Although Alzheimer’s pathology has been a frequent finding, recent advances in immunostaining of 
-synuclein have suggested the possible importance of cortical Lewy bodies (CLBs) in the brains of demented patients with PD.
METHODS: The brains of 22 demented and 20 nondemented patients with a clinical and neuropathologic diagnosis of PD were evaluated with standard neuropathologic techniques. In addition, CLBs and dystrophic neurites were identified immunohistochemically with antibodies specific for -synuclein and ubiquitin; plaques and tangles were identified by staining with thioflavine S. Associations between dementia status and pathologic markers were tested with logistic regression.
RESULTS: CLBs positive for -synuclein are highly sensitive (91%) and specific (90%) neuropathologic markers of dementia in PD and slightly more sensitive than ubiquitin-positive CLBs. They are better indicators of dementia than neurofibrillary tangles, amyloid plaques, or dystrophic neurites.
CONCLUSION: CLBs detected by -synuclein antibodies in patients with PD are a more sensitive and specific correlate of dementia than the presence of Alzheimer’s pathology, which was present in a minority of the cases in this series.
Key words: Lewy body—Dementia—PD—AD—-Synuclein—Ubiquitin.
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