Abstract
Aberrant sterol lipid metabolism is associated with physiological dysfunctions in the aging brain and aging-dependent disorders such as neurodegenerative diseases. There is an unmet demand to comprehensively profile sterol lipids spatially and temporally in different brain regions during aging. Here, we develop an ion mobility-mass spectrometry based four-dimensional sterolomics technology leveraged by a machine learning-empowered high-coverage library (>2000 sterol lipids) for accurate identification. We apply this four-dimensional technology to profile the spatially resolved landscapes of sterol lipids in ten functional regions of the mouse brain, and quantitatively uncover ~200 sterol lipids uniquely distributed in specific regions with concentrations spanning up to 8 orders of magnitude. Further spatial analysis pinpoints age-associated differences in region-specific sterol lipid metabolism, revealing changes in the numbers of altered sterol lipids, concentration variations, and age-dependent coregulation networks. These findings will contribute to our understanding of abnormal sterol lipid metabolism and its role in brain diseases.
Highlights
Aberrant sterol lipid metabolism is associated with physiological dysfunctions in the aging brain and aging-dependent disorders such as neurodegenerative diseases
Mounting evidence shows that aberrant sterol lipid metabolism in the brain is tightly linked to brain aging[10] and aging-dependent neurodegenerative diseases, such as Alzheimer’s disease (AD)[11,12,13], Parkinson’s disease (PD)[14], and Huntington’s disease (HD)[6]
Taking the isomer pair of epiandrosterone and etiocholanone as an example, the collision cross-section (CCS) difference between the two isomers was enlarged from 0.4% to 12.8% after derivatization (Fig. 2a)
Summary
Aberrant sterol lipid metabolism is associated with physiological dysfunctions in the aging brain and aging-dependent disorders such as neurodegenerative diseases. Further spatial analysis pinpoints age-associated differences in region-specific sterol lipid metabolism, revealing changes in the numbers of altered sterol lipids, concentration variations, and agedependent coregulation networks. These findings will contribute to our understanding of abnormal sterol lipid metabolism and its role in brain diseases. Cholesterol can be synthesized only in situ and serves as the metabolic precursor for conversion to other important sterol lipids such as oxysterols, steroid hormones, and vitamin D2,8,9.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
