Using Fatty Acid-Binding Proteins as Potential Biomarkers to Discriminate between Parkinson's Disease and Dementia with Lewy Bodies: Exploration of a Novel Technique

Abstract

An increase in the global aging population is leading to an increase in age-related conditions such as dementia and movement disorders, including Alzheimer's disease (AD), Parkinson's disease (PD), and dementia with Lewy bodies (DLB). The accurate prediction of risk factors associated with these disorders is crucial for early diagnosis and prevention. Biomarkers play a significant role in diagnosing and monitoring diseases. In neurodegenerative disorders like α-synucleinopathies, specific biomarkers can indicate the presence and progression of disease. We previously demonstrated the pathogenic impact of fatty acid-binding proteins (FABPs) in α-synucleinopathies. Therefore, this study investigated FABPs as potential biomarkers for Lewy body diseases. Plasma FABP levels were measured in patients with AD, PD, DLB, and mild cognitive impairment (MCI) and healthy controls. Plasma FABP3 was increased in all groups, while the levels of FABP5 and FABP7 tended to decrease in the AD group. Additionally, FABP2 levels were elevated in PD. A correlation analysis showed that higher FABP3 levels were associated with decreased cognitive function. The plasma concentrations of Tau, GFAP, NF-L, and UCHL1 correlated with cognitive decline. A scoring method was applied to discriminate between diseases, demonstrating high accuracy in distinguishing MCI vs. CN, AD vs. DLB, PD vs. DLB, and AD vs. PD. The study suggests that FABPs could serve as potential biomarkers for Lewy body diseases and aid in early disease detection and differentiation.

Keywords: Parkinson’s disease; biomarkers; dementia; dementia with Lewy bodies; diagnosis; discrimination technique; fatty acid-binding proteins; α-synucleinopathies.

Figure 1

The propagation of pathogenic α−synuclein and the modulation of plasma fatty acid−binding proteins (FABPs). (A) Schematic diagram illustrating the gut−to−axis propagation of pathogenic proteins, specifically α−synuclein, in Lewy bodies. (B) Alterations in plasma levels of FABP2, FABP3, FABP5, and FABP7 in different groups, including healthy controls (CN in black color), patients with mild cognitive impairment (MCI in green), Alzheimer’s disease (AD in red), Parkinson’s disease (PD in orange), and Dementia with Lewy bodies (DLB in blue). Data were analyzed using the Kruskal–Wallis test, followed by Dunn’s multiple comparison test. * p < 0.05, ** p < 0.01, *** p < 0.001, and **** p < 0.0001.

Figure 2

Alterations in the plasma levels of general biomarkers. The figure illustrates the plasma concentrations of α-synuclein, amyloid β 42 (Aβ42), total Tau, GFAP, NF-L, and UCHL1, highlighting the pathological changes associated with these biomarkers. Data were analyzed via the Kruskal–Wallis test, followed by Dunn’s multiple comparison test. * p < 0.05, ** p < 0.01, *** p < 0.001, and **** p < 0.0001. In the figure, CN is shown in black, MCI in green, AD in red, PD in orange, and DLB in blue.

Figure 3

Correlation analysis between various plasma biomarkers and the Mini−Mental State Examination (MMSE). The plasma concentrations of FABP3, total Tau, GFAP, NF−L, and UCHL1 are shown. The correlation diagrams demonstrate the relationship between the MMSE and FABP3, Tau, GFAP, NF−L, and UCHL1, as well as age. Correlation coefficients (R values) ranging from 0.8 to 1.0, from 0.5 to 0.8, and from 0.2 to 0.5 were categorized as strong, moderate, and weak correlations, respectively. In the correlation analyses, the p−values for all analyzed groups were p < 0.0001.

Figure 4

Comparison of score values and accuracy for each quantified disease group. The figure displays the comparison of quantified score values for different disease groups, including (A) MCI vs. CN, (B) AD vs. DLB, (C) PD vs. DLB, and (D) AD vs. PD, as well as within each individual group. In the right column, the accuracy of the quantified score values was assessed using receiver operating characteristic (ROC) curves. ROC curves for (A) MCI vs. CN, (B) AD vs. DLB, (C) PD vs. DLB, and (D) AD vs. PD are presented, demonstrating the performance and discriminative ability of the quantified scores. Data were analyzed via the Kruskal–Wallis test, followed by Dunn’s multiple comparison test to compare each disease group. * p < 0.05, ** p < 0.01, *** p < 0.001, and **** p < 0.0001. In the figure, CN is shown in black, MCI in green, AD in red, PD in orange, and DLB in blue.