| Summary: | Biomarkers are increasingly recognized as tools in the diagnosis and prognosis of neurodegenerative diseases. No fluid biomarker for Parkinson’s disease (PD) has been established to date, but α-synuclein, a major component of Lewy bodies in PD and dementia with Lewy bodies (DLB), has become a promising candidate. Here, we investigated CSF α-synuclein in patients with PD (<i>n</i> = 28), PDD (<i>n</i> = 8), and DLB (<i>n</i> = 5), applying an electrochemiluminescence immunoassay. Median values were non-significantly (<i>p</i> = 0.430) higher in patients with PDD and DLB (287 pg/mL) than in PD (236 pg/mL). A group of <i>n</i> = 36 primarily non-demented patients with PD and PDD was clinically followed for up to two years. A higher baseline α-synuclein was associated with increases in Hoehn and Yahr classifications (<i>p</i> = 0.019) and Beck Depression Inventory scores (<i>p</i> < 0.001) as well as worse performance in Trail Making Test A (<i>p</i> = 0.017), Trail Making Test B (<i>p</i> = 0.043), and the Boston Naming Test (<i>p</i> = 0.002) at follow-up. Surprisingly, higher levels were associated with a better performance in semantic verbal fluency tests (<i>p</i> = 0.046). In summary, CSF α-synuclein may be a potential prognostic marker for disease progression, affective symptoms, and executive cognitive function in PD. Larger-scaled studies have to validate these findings and the discordant results for single cognitive tests in this exploratory investigation.
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