Mass spectrometry imaging highlights dynamic patterns of lipid co-expression with Aβ plaques in mouse and human brains
Lipids play crucial roles in the susceptibility and brain cellular responses to Alzheimer's disease (AD) and are increasingly considered potential soluble biomarkers in cerebrospinal fluid (CSF) and plasma. To delineate the pathological correlations of distinct lipid species, we conducted a com...
| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Journal Article |
| Language: | English |
| Published: |
2024
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| Online Access: | https://hdl.handle.net/10356/179950 |
| _version_ | 1824456312421875712 |
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| author | Huang, Helen Xuexia Inglese, Paolo Tang, Jiabin Yagoubi, Riad Correia, Gonçalo D. S. Horneffer-van der Sluis, Verena M. Camuzeaux, Stephane Wu, Vincen Kopanitsa, Maksym V. Willumsen, Nanet Jackson, Johanna S. Barron, Anna M. Saito, Takashi Saido, Takaomi C. Gentlemen, Steve Takats, Zoltan Matthews, Paul M. |
| author2 | Lee Kong Chian School of Medicine (LKCMedicine) |
| author_facet | Lee Kong Chian School of Medicine (LKCMedicine) Huang, Helen Xuexia Inglese, Paolo Tang, Jiabin Yagoubi, Riad Correia, Gonçalo D. S. Horneffer-van der Sluis, Verena M. Camuzeaux, Stephane Wu, Vincen Kopanitsa, Maksym V. Willumsen, Nanet Jackson, Johanna S. Barron, Anna M. Saito, Takashi Saido, Takaomi C. Gentlemen, Steve Takats, Zoltan Matthews, Paul M. |
| author_sort | Huang, Helen Xuexia |
| collection | NTU |
| description | Lipids play crucial roles in the susceptibility and brain cellular responses to Alzheimer's disease (AD) and are increasingly considered potential soluble biomarkers in cerebrospinal fluid (CSF) and plasma. To delineate the pathological correlations of distinct lipid species, we conducted a comprehensive characterization of both spatially localized and global differences in brain lipid composition in AppNL-G-F mice with spatial and bulk mass spectrometry lipidomic profiling, using human amyloid-expressing (h-Aβ) and WT mouse brains controls. We observed age-dependent increases in lysophospholipids, bis(monoacylglycerol) phosphates, and phosphatidylglycerols around Aβ plaques in AppNL-G-F mice. Immunohistology-based co-localization identified associations between focal pro-inflammatory lipids, glial activation, and autophagic flux disruption. Likewise, in human donors with varying Braak stages, similar studies of cortical sections revealed co-expression of lysophospholipids and ceramides around Aβ plaques in AD (Braak stage V/VI) but not in earlier Braak stage controls. Our findings in mice provide evidence of temporally and spatially heterogeneous differences in lipid composition as local and global Aβ-related pathologies evolve. Observing similar lipidomic changes associated with pathological Aβ plaques in human AD tissue provides a foundation for understanding differences in CSF lipids with reported clinical stage or disease severity. |
| first_indexed | 2025-02-19T03:52:06Z |
| format | Journal Article |
| id | ntu-10356/179950 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2025-02-19T03:52:06Z |
| publishDate | 2024 |
| record_format | dspace |
| spelling | ntu-10356/1799502024-09-08T15:38:10Z Mass spectrometry imaging highlights dynamic patterns of lipid co-expression with Aβ plaques in mouse and human brains Huang, Helen Xuexia Inglese, Paolo Tang, Jiabin Yagoubi, Riad Correia, Gonçalo D. S. Horneffer-van der Sluis, Verena M. Camuzeaux, Stephane Wu, Vincen Kopanitsa, Maksym V. Willumsen, Nanet Jackson, Johanna S. Barron, Anna M. Saito, Takashi Saido, Takaomi C. Gentlemen, Steve Takats, Zoltan Matthews, Paul M. Lee Kong Chian School of Medicine (LKCMedicine) Medicine, Health and Life Sciences Alzheimer's disease Autophagic disruption Lipids play crucial roles in the susceptibility and brain cellular responses to Alzheimer's disease (AD) and are increasingly considered potential soluble biomarkers in cerebrospinal fluid (CSF) and plasma. To delineate the pathological correlations of distinct lipid species, we conducted a comprehensive characterization of both spatially localized and global differences in brain lipid composition in AppNL-G-F mice with spatial and bulk mass spectrometry lipidomic profiling, using human amyloid-expressing (h-Aβ) and WT mouse brains controls. We observed age-dependent increases in lysophospholipids, bis(monoacylglycerol) phosphates, and phosphatidylglycerols around Aβ plaques in AppNL-G-F mice. Immunohistology-based co-localization identified associations between focal pro-inflammatory lipids, glial activation, and autophagic flux disruption. Likewise, in human donors with varying Braak stages, similar studies of cortical sections revealed co-expression of lysophospholipids and ceramides around Aβ plaques in AD (Braak stage V/VI) but not in earlier Braak stage controls. Our findings in mice provide evidence of temporally and spatially heterogeneous differences in lipid composition as local and global Aβ-related pathologies evolve. Observing similar lipidomic changes associated with pathological Aβ plaques in human AD tissue provides a foundation for understanding differences in CSF lipids with reported clinical stage or disease severity. Published version This work is funded by the UK Dementia Research Institute (to PMM), which receives funding from UK DRI Ltd, funded by the UK Medical Research Council, Alzheimer's Society, and Alzheimer's Research UK. 2024-09-04T07:18:09Z 2024-09-04T07:18:09Z 2024 Journal Article Huang, H. X., Inglese, P., Tang, J., Yagoubi, R., Correia, G. D. S., Horneffer-van der Sluis, V. M., Camuzeaux, S., Wu, V., Kopanitsa, M. V., Willumsen, N., Jackson, J. S., Barron, A. M., Saito, T., Saido, T. C., Gentlemen, S., Takats, Z. & Matthews, P. M. (2024). Mass spectrometry imaging highlights dynamic patterns of lipid co-expression with Aβ plaques in mouse and human brains. Journal of Neurochemistry, 168(7), 1193-1214. https://dx.doi.org/10.1111/jnc.16042 0022-3042 https://hdl.handle.net/10356/179950 10.1111/jnc.16042 38372586 2-s2.0-85185669770 7 168 1193 1214 en Journal of Neurochemistry © 2024 The Authors. Journal of Neurochemistry published by John Wiley & Sons Ltd on behalf of International Society for Neurochemistry. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. application/pdf |
| spellingShingle | Medicine, Health and Life Sciences Alzheimer's disease Autophagic disruption Huang, Helen Xuexia Inglese, Paolo Tang, Jiabin Yagoubi, Riad Correia, Gonçalo D. S. Horneffer-van der Sluis, Verena M. Camuzeaux, Stephane Wu, Vincen Kopanitsa, Maksym V. Willumsen, Nanet Jackson, Johanna S. Barron, Anna M. Saito, Takashi Saido, Takaomi C. Gentlemen, Steve Takats, Zoltan Matthews, Paul M. Mass spectrometry imaging highlights dynamic patterns of lipid co-expression with Aβ plaques in mouse and human brains |
| title | Mass spectrometry imaging highlights dynamic patterns of lipid co-expression with Aβ plaques in mouse and human brains |
| title_full | Mass spectrometry imaging highlights dynamic patterns of lipid co-expression with Aβ plaques in mouse and human brains |
| title_fullStr | Mass spectrometry imaging highlights dynamic patterns of lipid co-expression with Aβ plaques in mouse and human brains |
| title_full_unstemmed | Mass spectrometry imaging highlights dynamic patterns of lipid co-expression with Aβ plaques in mouse and human brains |
| title_short | Mass spectrometry imaging highlights dynamic patterns of lipid co-expression with Aβ plaques in mouse and human brains |
| title_sort | mass spectrometry imaging highlights dynamic patterns of lipid co expression with aβ plaques in mouse and human brains |
| topic | Medicine, Health and Life Sciences Alzheimer's disease Autophagic disruption |
| url | https://hdl.handle.net/10356/179950 |
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