Metabolomic Profiling of Bile Acids in an Experimental Model of Prodromal Parkinson's Disease

Abstract

For people with Parkinson's disease (PD), considered the most common neurodegenerative disease behind Alzheimer's disease, accurate diagnosis is dependent on many factors; however, misdiagnosis is extremely common in the prodromal phases of the disease, when treatment is thought to be most effective. Currently, there are no robust biomarkers that aid in the early diagnosis of PD. Following previously reported work by our group, we accurately measured the concentrations of 18 bile acids in the serum of a prodromal mouse model of PD. We identified three bile acids at significantly different concentrations (p < 0.05) when mice representing a prodromal PD model were compared with controls. These include ω-murichoclic acid (MCAo), tauroursodeoxycholic acid (TUDCA) and ursodeoxycholic acid (UDCA). All were down-regulated in prodromal PD mice with TUDCA and UDCA at significantly lower levels (17-fold and 14-fold decrease, respectively). Using the concentration of three bile acids combined with logistic regression, we can discriminate between prodromal PD mice from control mice with high accuracy (AUC (95% CI) = 0.906 (0.777⁻1.000)) following cross validation. Our study highlights the need to investigate bile acids as potential biomarkers that predict PD and possibly reflect the progression of manifest PD.

Keywords: bile acids; biomarkers; mass spectrometry; prodromal Parkinson’s disease; α-synuclein aggregates.

Figure 1

The mean distribution (±SEM) for each of the three significantly different bile acids between mice injected with HuMonomers and PFFs.

Figure 2

The ROC plot for the logistic regression diagnostic algorithm.

Figure 3

Depiction of Bile Acid Metabolism in the liver and gut of mice. Bile acids outlined in blue are neuroprotective, bile acids outlined in red are cytotoxic and those bile acids in red with an accompanying asterisk are statistically significantly different between HuMonomer- and PFF-injected mice. The section detailing Muricholic acid (MCA) only occurs in mice.