Mass spectrometry imaging highlights dynamic patterns of lipid co-expression with Aβ plaques in mouse and human brains

被引:6
作者
Huang, Helen Xuexia [1 ,2 ]
Inglese, Paolo [1 ,3 ]
Tang, Jiabin [4 ]
Yagoubi, Riad [1 ,2 ]
Correia, Goncalo D. S. [1 ,3 ]
Horneffer-van der Sluis, Verena M. [3 ]
Camuzeaux, Stephane [3 ]
Wu, Vincen [1 ]
Kopanitsa, Maksym V. [2 ]
Willumsen, Nanet [2 ,4 ]
Jackson, Johanna S. [2 ,4 ]
Barron, Anna M. [5 ]
Saito, Takashi [6 ,7 ]
Saido, Takaomi C. [6 ,7 ]
Gentlemen, Steve [4 ]
Takats, Zoltan [1 ,8 ]
Matthews, Paul M. [2 ,4 ,9 ]
机构
[1] Imperial Coll London, Dept Metab Digest & Reprod, Sect Bioanalyt Chem, London, England
[2] Imperial Coll London, UK Dementia Res Inst, London, England
[3] Imperial Coll London, Natl Phenome Ctr, Dept Metab Digest & Reprod, London, England
[4] Imperial Coll London, Dept Brain Sci, London, England
[5] Nanyang Technol Univ, Lee Kong Chian Sch Med, Singapore, Singapore
[6] RIKEN, Ctr Brain Sci, Lab Proteolyt Neurosci, Saitama, Japan
[7] Nagoya City Univ, Inst Brain Sci, Dept Neurocognit Sci, Grad Sch Med Sci, Nagoya, Aichi, Japan
[8] Imperial Coll London, Dept Metab Digest & Reprod, Sect Bioanalyt Chem, Hammersmith Campus, London SW7 2AZ, England
[9] Imperial Coll London, UK Dementia Res Inst Imperial Coll London, Uren Bldg, White City Campus, London W12 0BZ, England
基金
英国医学研究理事会;
关键词
Alzheimer's disease; autophagic disruption; A beta plaques; network analysis; pro-inflammatory lipids; spatial lipidomics; ALZHEIMERS-DISEASE; AMYLOID PLAQUES; PATHOLOGY; PROTEIN; MODELS; PHOSPHOLIPIDS; ASSOCIATION; TRANSPORTER; EXPRESSION; PACKAGE;
D O I
10.1111/jnc.16042
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 App(NL-G-F) mice with spatial and bulk mass spectrometry lipidomic profiling, using human amyloid-expressing (h-A beta) and WT mouse brains controls. We observed age-dependent increases in lysophospholipids, bis(monoacylglycerol) phosphates, and phosphatidylglycerols around A beta plaques in App(NL-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 A beta 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 A beta-related pathologies evolve. Observing similar lipidomic changes associated with pathological A beta plaques in human AD tissue provides a foundation for understanding differences in CSF lipids with reported clinical stage or disease severity.
引用
收藏
页码:1193 / 1214
页数:22
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