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, Aβ1-42 and tau from seventy-seven non-demented PD and thirty control participants. CSF α-syn and Aβ1-42 were significantly lower in PD compared to controls. In contrast to 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 to 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.

Neuroimaging biomarkers for Parkinson disease: Facts and fantasy

“…80 CSF Aβ 1-42 inversely correlated with PiB mean cortical binding potential, with PiB positive PD participants having lower CSF Aβ 1-42 compared to PiB negative PD participants. Furthermore, CSF α-synuclein 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.…”

Group comparison of spatiotemporal dynamics of intrinsic networks in Parkinson’s disease

“…It is unclear whether CSF total tau decreases (Zhang et al, 2008;Kang et al, 2013) or remains unchanged in Parkinson's disease (Buddhala et al, 2015), and therefore difficult to predict how CSF levels of tau might relate to network disruption. Therefore our investigations of tau and tau-P181 and network disruption are exploratory.…”

“…Newer PET imaging agents for pathological tau are now coming into widespread use, while imaging probes for a-synuclein are still under development. Thus CSF biomarkers currently offer the most comprehensive approach to anchor an analysis of systems alterations to pathophysiological processes of Alzheimer's or Parkinson's diseases (Montine et al, 2010;Stewart et al, 2014;Buddhala et al, 2015).…”

CSF biomarkers in neurodegenerative and vascular dementias

“…In the same line, a recent study demonstrates that decreased Ab42 levels predict early-onset dementia in PD (Alves et al, 2014). Although CSF tau is not sufficient to discriminate PD (Buddhala et al, 2015), the combination of a-synuclein and tau levels seems to be useful in PD, as low CSF levels of both tau and a-synuclein have been reported in PD compared to controls (Kang et al, 2013). A positive correlation between tau and a-synuclein levels has also been reported in another study (Parnetti et al, 2014).…”