Objective: The present study investigated alterations of circulatory lipoprotein profiles, including cholesterol, triglycerides (TGs), phospholipids (PLs) and apolipoproteins (Apo) in lipoprotein subfractions, in Parkinson’s disease (PD) patients using nuclear magnetic resonance (NMR) spectroscopy-based metabolomics.

Background: Patients with PD  may have abnormal lipid metabolism. Disturbances in lipid composition and lipoprotein metabolism play a crucial role in the pathogenesis of PD. To date, a complete picture of lipoprotein profiles in PD remains elusive.

Method: Nuclear magnetic resonance (NMR) spectroscopy with analysis tools was applied to measure the lipoprotein profiles in the plasma of 57 healthy controls, 72 PD patients with early PD (ePD, Hoehn-Yahr stage ≤ 2), and 21 patients with advanced PD (aPD, Hoehn &Yahr stage > 2). The lipoprotein profiles included biochemical components of total cholesterol, free cholesterol (FC), phospholipids (PLs), triglycerides (TGs), apolipoproteins (Apo) A1/A2/B, and particle number (PN) in different density lipoproteins (high-density lipoprotein [HDL]-1,2,3,4, low density lipoprotein (LDL)-1,2,3,4,5,6, and very low-density lipoprotein [VLDL]-1,2,3,4,5) in the 112 lipoprotein subfractions and components.

Results: Significant changes were found in 10 lipoprotein subfractions and components. Three subfractions, including total cholesterol, Apo-A1, and Apo-A2 in HDL-4 (HDL-4-C, HDL-4-Apo-A1, HDL-4-Apo-A2), total cholesterol, PLs, Apo-B and PN in LDL-6 (LDL-6-C, LDL-6-PL, LDL-6-Apo-B, and LDL-6-PN), and total cholesterol, FC and PLs in LDL-5 (LDL-5-C, LDL-5-FC, and LDL-5-PL), demonstrated the lowest levels in aPD patients compared with ePD patients and controls. These metabolic parameters showed significant correlations with clinical scales of motor disability, cognitive dysfunction, and depression. Analyses of receiver operating characteristic (ROC) curves for HDL-4-Apo-A1 (AUC: 0.784), HDL-4-Apo-A2 (AUC: 0.754), and HDL-4-C (AUC: 0.741) demonstrated better ability than alpha-synuclein (0.629) alone to separate aPD from ePD.

Conclusion: NMR-based lipoprotein profiling analysis demonstrates substantial evidence to support the involvement of lipids and apolipoproteins in PD and unravels a pathogenic redistribution of the lipoprotein profiles in PD patients. Cholesterol, Apo-A1, and Apo-A2 in HDL-4 subfractions may be biomarkers for aPD.

References: Jin U, Park SJ, Park SM. Cholesterol Metabolism in the Brain and Its Association with Parkinson’s Disease. Exp Neurobiol 2019;28:554-567.
Fang F, Zhan Y, Hammar N, et al. Lipids, Apolipoproteins, and the Risk of Parkinson Disease. Circ Res 2019;125:643-652.
Park JH, Lee CW, Nam MJ, et al. Association of High-Density Lipoprotein Cholesterol Variability and the Risk of Developing Parkinson Disease. Neurology 2021;96:e1391-e1401.
Rozani V, Gurevich T, Giladi N, et al. Higher serum cholesterol and decreased Parkinson’s disease risk: A statin-free cohort study. Mov Disord 2018;33:1298-1305.
Zhang L, Wang X, Wang M, et al. Circulating Cholesterol Levels May Link to the Factors Influencing Parkinson’s Risk. Front Neurol 2017;8:501.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/reduced-plasma-levels-of-small-hdl-subfractions-in-advanced-parkinsons-disease/