Alpha-synuclein cortical Lewy bodies correlate with dementia in Parkinson's disease

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. Al though Alzheimer's pathology has been a frequent finding, recent advances i n immunostaining of alpha-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 clini cal and neuropathologic diagnosis of PD were evaluated with standard neurop athologic techniques. In addition, CLBs and dystrophic neurites were identi fied immunohistochemically with antibodies specific for alpha-synuclein and ubiquitin; plaques and tangles were identified by staining with thioflavin e S. Associations between dementia status and pathologic markers were teste d with logistic regression. Results: CLBs positive for alpha-synuclein are highly sensitive (91%) and specific (90%) neuropathologic markers of dement ia in PD and slightly more sensitive than ubiquitin-positive CLBs. They are better indicators of dementia than neurofibrillary tangles, amyloid plaque s, or dystrophic neurites. Conclusion: CLBs detected by alpha-synuclein ant ibodies 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.