Correlation between decreased CSF α-synuclein and Aβ_1-42 in Parkinson disease

Accumulation of misfolded α-synuclein (α-syn) protein in Lewy bodies and neurites is the cardinal pathologic feature of Parkinson disease (PD), but abnormal deposition of other proteins may also play a role. Cerebrospinal fluid (CSF) levels of proteins known to accumulate in PD may provide insight into disease-associated changes in protein metabolism and their relationship to disease progression. We measured CSF α-syn, amyloid β_1-42 (Aβ_1-42), and tau from 77 nondemented PD and 30 control participants. CSF α-syn and Aβ_1-42 were significantly lower in PD compared with controls. In contrast with increased CSF tau in Alzheimer disease, CSF tau did not significantly differ between PD and controls. CSF protein levels did not significantly correlate with ratings of motor function or performance on neuropsychological testing. As expected, CSF Aβ_1-42 inversely correlated with [¹¹C]-Pittsburgh compound B (PiB) mean cortical binding potential, with PiB⁺ PD participants having lower CSF Aβ_1-42 compared with PiB^- PD participants. Furthermore, CSF α-syn positively correlated with Aβ_1-42 in PD participants but not in controls, suggesting a pathophysiologic connection between the metabolisms of these proteins in PD.