Exploring Lipid Disturbances and its Spatial Association with α-Synuclein Aggregation in MSA Patient Brain Regions via Desorption Electrospray Ionization Mass Spectrometry Imaging
Ching-Yao Chang1, Ming-Che Kuo2, Yufeng Tseng1
1National Taiwan University, 2National Taiwan University Hospital
Objective:
In this study, we assessed the utility of DESI-MSI for the analysis of lipid disturbances in brain tissues related to Multiple system atrophy (MSA) using a straightforward sample preparation method that minimizes tissue damage. Additionally, this study aimed to investigate the spatial distribution of lipids within various brain regions impacted by MSA and determine any potential correlations between lipid distribution and the presence of α-synuclein.
Background:
Multiple system atrophy (MSA) is a rare neurodegenerative disease categorized as a synucleinopathy characterized by the abnormal accumulation of α-synuclein. Lipids changes have been observed in MSA patients' biofluids, such as plasma and cerebrospinal fluid. However, understanding the spatial distribution of these metabolites in different brain regions is still limited.
Design/Methods:
Desorption electrospray ionization mass spectrometry imaging (DESI-MSI) is a soft ionization technique that can identify and visualize the distribution of molecules in tissues. Here, we applied DESI-MSI to 12 different regions of human brain tissues, including the prefrontal cortex, orbitofrontal cortex, motor cortex, sensory cortex, occipital cortex, corpus callosum, uncinate fascicle, thalamus, putamen, caudate, vermis, and cerebrocerebellum, thus covering most of the affected brain regions in MSA patients.
Results:
We compared the lipid expression of fresh frozen samples and investigated the distribution of the altered lipids. Additionally, we used immunohistochemistry (IHC) staining to visualize the spatial distribution of α-synuclein. We performed image registration of histological images and mass spectrometry images to explore the correlation between the distribution of α-synuclein and the identified lipids.
Conclusions:
Our findings demonstrated the utility of DESI-MSI in analyzing MSA-related lipid disturbances in brain tissues with a simple sample preparation process and minimal tissue damage. Moreover, our study provides insight into the spatial distribution of lipids in different brain regions affected by MSA and their correlation with the distribution of α-synuclein.