Correlation between decreased CSF α-synuclein and Aβ1–42 in Parkinson disease

Abstract

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 β1–42 (Aβ1–42), and tau from 77 nondemented PD and 30 control participants. CSF α-syn and Aβ1–42 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 Aβ1–42 inversely correlated with [11C]-Pittsburgh compound B (PiB) mean cortical binding potential, with PiB+ PD participants having lower CSF Aβ1–42 compared with PiB− PD participants. Furthermore, CSF α-syn positively correlated with Aβ1–42 in PD participants but not in controls, suggesting a pathophysiologic connection between the metabolisms of these proteins in PD.