Elevated ApoE, ApoJ and lipoprotein-bound α-synuclein levels in cerebrospinal fluid from Parkinson's disease patients - Validation in the BioFIND cohort

Abstract

Background: The progressive accumulation, aggregation, and spread of α-synuclein (aSN) are common hallmarks of Parkinson's disease (PD) pathology. The genotype of apolipoprotein E (ApoE) influences PD progression. Recently we found that aSN co-localize with apolipoproteins on lipoprotein vesicles. We reported an increased level of ApoE, ApoJ and lipoprotein-bound aSN in CSF from early PD patients compared to matched controls. We also found reduced plasma ApoAI in PD patients.

Objective: In this study, we used the same approach on the BioFIND cohort to validate our previous results and extended the studies to examine correlations with ApoE genotype, demographic variables, clinical symptoms and other biochemical findings reported in the BioFIND cohort.

Methods: For the assessment, we used Western-Blot (WB) technique for apolipoproteins measurements in CSF and plasma from PD patients and healthy controls. Further, for measurement of aSN bound to lipoproteins, we combined immunodepletion with the enzyme-linked immunosorbent assay (ELISA).

Results: Levels of ApoE, ApoJ and lipoprotein bound aSN were significantly increased in CSF from PD patients compared to controls. We also observed decreased levels of ApoAI and ApoJ in plasma from PD patients compared to controls.

Conclusions: Concluding, the present data validated our previous findings. Altered lipoproteins appear to be important in early PD pathology and may be involved in mechanisms underlying aSN cell-to-cell transfer in the nervous system and be developed in algorithms for early diagnosis of PD.

Keywords: Apolipoproteins; Cerebrospinal fluid; Lipoproteins; Parkinson's disease; α-synuclein.