INTRODUCTION: The objective was to study whether alpha-synuclein oligomers are altered in the cerebrospinal fluid (CSF) of patients with dementia, including Parkinson disease with dementia (PDD), dementia with Lewy bodies (DLB), and Alzheimer disease (AD), compared with age-matched controls. METHODS: In total, 247 CSF samples were assessed in this study, including 71 patients with DLB, 30 patients with PDD, 48 patients with AD, and 98 healthy age-matched controls. Both total and oligomeric alpha-synuclein levels were evaluated by using well-established immunoassays. RESULTS: The levels of alpha-synuclein oligomers in the CSF were increased in patients with PDD compared with the controls (P < 0.05), but not in patients with DLB compared with controls. Interestingly, the levels of alpha-synuclein oligomers in the CSF were also significantly higher in patients with PDD (P < 0.01) and DLB (P < 0.05) compared with patients with AD. The levels of CSF alpha-synuclein oligomers and the ratio of oligomeric/total-alpha-synuclein could distinguish DLB or PDD patients from AD patients, with areas under the curves (AUCs) of 0.64 and 0.75, respectively. In addition, total-alpha-synuclein alone could distinguish DLB or PDD patients from AD patients, with an AUC of 0.80. CONCLUSIONS: The levels of alpha-synuclein oligomers were increased in the CSF from alpha-synucleinopathy patients with dementia compared with AD cases.