DJ-1 and αSYN in LRRK2 CSF do not correlate with striatal dopaminergic function

Abstract

Previous studies demonstrated decreased levels of DJ-1 and α-synuclein (αSYN) in human cerebrospinal fluid (CSF) in patients with Parkinson’s disease (PD), but neither marker correlated with PD severity, raising the possibility that they may be excellent progression markers during early or preclinical phases of PD. Individuals carrying the leucine-rich repeat kinase 2 (LRRK2) gene mutation are at increased risk for PD, and the phenotype of LRRK2 patients is almost identical to sporadic PD. To determine whether dopaminergic dysfunction in the basal ganglia, as determined by positron emission tomography (PET) scans, correlates with CSF levels of DJ-1 and αSYN during preclinical stages, Luminex assays were used to analyze CSF samples from asymptomatic LRRK2 mutation carriers, along with carriers who presented with a clinical diagnosis of PD. The data revealed no statistically significant relationship between PET scan evidence of loss of striatal dopaminergic function and the CSF biomarkers DJ-1 and αSYN, except for a weak correlation between DJ-1 and MP binding, suggesting that the use of these potential biomarkers on their own to screen LRRK2 gene mutation carriers for PD is not appropriate.

Cerebrospinal fluid biochemical studies in patients with Parkinson's disease: toward a potential search for biomarkers for this disease

“…In addition, a recent study by Shi et al (2012) described a lack of relation between the loss of striatal dopaminergic function, assessed by positron emission tomography (PET), and CSF α-synuclein levels, in asymptomatic carriers of mutations in the LRRK2 gene. CSF neurosin (a protease that degrades α-synuclein) levels have been found to be decreased (Wennström et al, 2013).…”

Motor deficits associated with changes in -amyloid in Parkinson's disease

“…In particular, reduced striatal dopamine function strongly correlates with reduced CSF Aβ proteins3 rather than CSF α-synuclein levels4 in these preclinical LRRK2 cases. In sporadic PD, many studies have shown correlations between reduced CSF Aβ and cognitive impairment and more rapid cognitive decline,5–8 particularly with deficits in verbal fluency which may have a motor component.…”

Proteomic profiling in MPTP monkey model for early Parkinson disease biomarker discovery

“…Thus, a current major focus of early PD biomarker research is to identify biochemical marker candidates in the brain or body fluids, which might reflect the state of the disease. We have already investigated several potential cerebrospinal fluid (CSF) markers (known to be important in sporadic PD) in a cohort of symptomatic and asymptomatic subjects carrying one of the strongest risk factors for PD - the leucine rich repeat kinase 2 ( LRRK2 ) gene mutations, and identified that some CSF protein levels correlated with the progressive loss of striatal dopaminergic functions as determined by positron emission tomography (PET) [8, 9]. The emergence of several –omics techniques, including transcriptomics, proteomics and metabolomics, has also greatly enhanced our ability to identify novel pathways and potential biomarkers for PD [7, 10, 11].…”