Objective: To perform a lipidomic profile in serum samples from IRBD patients collected before and after their conversion to PD and DLB, in order to identify possible biomarkers for risk, onset or disease progression.

Background: Long-term prospective studies have shown that most patients with IRBD will eventually develop a synucleinopathy [1]. The specificity and positive predictive value of IRBD seems to be much higher than any other features of the prodromal phase of these diseases [2]. Metabolomic profiling has proved useful to study the pathophysiology and to identify biomarkers for a number of diseases, including PD [3,4]. We have focused specifically on the analysis of lipoprotein particles [5].

Method: The Liposcale test uses 2D diffusion-edited 1H nuclear magnetic resonance spectroscopy to estimate the sizes and the relative proportions of different lipoprotein subclasses, as well as the lipid content of the main classes [6]. We have profiled a total of 158 serum samples of individuals in different subgroups: IRBD patients before and after the actual phenotypic conversion to a synucleinopathy, IRBD patients that remained disease-free at the time of sample extraction, idiopathic Parkinson’s disease (iPD) patients and sex- and aged-matched control subjects (n=16-36 samples per group).

Results: In IRBD subjects we found increased levels of VLDL (28.4±12.1 vs 37.7±30.8 nm/L, p=0.031) and triglycerides (38.2±14 vs 53±39.5 mg/dl, p=0.031), decreased diameter of LDL particles (21.16±0.171 vs 21.064±0.21 nm, p=0.031), and decreased levels of HDL cholesterol (52.9±21.7 vs 44.3±20.5 mg/dl, p=0.078) after conversion to PD. In those IRBD that converted to DLB, we found decreased levels of LDL triglycerides (319.2±8.9 vs 13.6±5.5 mg/dl, p=0.005). In general, the manifestation of a synucleinopathy is associated with a profile compatible with higher cardiovascular disease risk.

Conclusion: Our data show that patients with IRBD present changes in their serum lipidomic profile that could be used as a blood-based biomarker panel for predicting their long-term conversion to either PD or DLB. Further validation studies in additional and larger cohorts are needed to determine the sensitivity and specificity of the possible biomarkers to identify individuals at risk of developing PD or DLB, and also to gain insight into the molecular pathogenesis of the disease.

References: [1] Iranzo, A. et al. Neurodegenerative disease status and post-mortem pathology in idiopathic rapid-eye-movement sleep behaviour disorder: an observational cohort study. Lancet. Neurol. 12, 443–53 (2013). [2] Iranzo, A. et al. Neuropathology of prodromal Lewy body disease. Mov. Disord. 29, 410–5 (2014). [3] Han, W., Sapkota, S., Camicioli, R., Dixon, R. A. & Li, L. Profiling novel metabolic biomarkers for Parkinson’s disease using in-depth metabolomic analysis. Mov. Disord. 32, 1720–1728 (2017). [4] Stoessel, D. et al. Promising metabolite profiles in the plasma and CSF of early clinical Parkinson’s Disease. Front. Aging Neurosci. 10, 51 (2018). [5] Sterling,N.W. et al. Higher plasma LDL-Cholesterol is associated with preserved executive and fine motor functions in Parkinson’s Disease. Aging and Disease 7 (3), 237-245 (2016). [6] Mallol, R. et al. Liposcale: a novel advanced lipoprotein test based on 2D diffusion-ordered 1H NMR spectroscopy. Journal of lipid research 56, 737–46 (2015).

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MDS Abstracts - https://www.mdsabstracts.org/abstract/profiling-of-lipoproteins-and-associated-lipids-in-serum-samples-from-idiopathic-rem-sleep-behavior-disorder-patients-to-identify-biomarkers-for-parkinsons-disease/