CoChat
Sign Up
Cited by 83Alzheimer's disease research and treatmentsMass Spectrometry Techniques and ApplicationsMetabolomics and Mass Spectrometry Studies

Global changes of phospholipids identified by MALDI imaging mass spectrometry in a mouse model of Alzheimer's disease

Open access
Hong, Ji Hye, Kang, Jeong Won, Kim, Dong Kyu, Baik, Sung Hoon, Kim, Kyung Ho, Shanta, Selina Rahman, Jung, Jae Hun, Mook-Jung, Inhee +1 more·2016·Journal of Lipid Research
DOI 10.1194/jlr.m057869PMC PMC4689334
Open this paper in CoChat — free account

Abstract

Alzheimer's disease (AD) is the most common form of dementia; however, at the present time there is no disease-modifying drug for AD. There is increasing evidence supporting the role of lipid changes in the process of normal cognitive aging and in the etiology of age-related neurodegenerative diseases. AD is characterized by the presence of intraneuronal protein clusters and extracellular aggregates of β-amyloid (Aβ). Disrupted Aβ kinetics may activate intracellular signaling pathways, including tau hyperphosphorylation and proinflammatory pathways. We analyzed and visualized the lipid profiles of mouse brains using MALDI-TOF MS. Direct tissue analysis by MALDI-TOF imaging MS (IMS) can determine the relative abundance and spatial distribution of specific lipids in different tissues. We used 5XFAD mice that almost exclusively generate and rapidly accumulate massive cerebral levels of Aβ-42 (1). Our data showed changes in lipid distribution in the mouse frontal cortex, hippocampus, and subiculum, where Aβ plaques are first generated in AD. Our results suggest that MALDI-IMS is a powerful tool for analyzing the distribution of various phospholipids and that this application might provide novel insight into the prediction of disease.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1194/jlr.m057869

Cites

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

No citation lists for this paper

No citation lists for this paper yet — checked again daily.

References 54 · Cited by 83

Research works printed but not linked: 49

  1. [2]2. Pimplikar, S.W. Reassessing the amyloid cascade hypothesis of Alzheimer's disease Int. J. Biochem. Cell Biol. 2009; 41:1261-1268 Crossref Scopus (322) PubMed Google Scholar
  2. [3]3. Borysova, L. ∙ Wray, S. ∙ Eisner, D.A. ... How calcium signals in myocytes and pericytes are integrated across in situ microvascular networks and control microvascular tone Cell Calcium. 2013; 54:163-174 Crossref Scopus (58) PubMed Google Scholar
  3. [4]4. Chai, Q. ∙ Wang, X.L. ∙ Zeldin, D.C. ... Role of caveolae in shear stress-mediated endothelium-dependent dilation in coronary arteries Cardiovasc. Res. 2013; 100:151-159 Crossref Scopus (35) PubMed Google Scholar
  4. [5]5. Kameritsch, P. ∙ Khandoga, N. ∙ Pohl, U. ... Gap junctional communication promotes apoptosis in a connexin-type-dependent manner Cell Death Dis. 2013; 4:e584 Crossref Scopus (75) PubMed Google Scholar
  5. [6]6. Bosche, B. ∙ Schafer, M. ∙ Graf, R. ... Lithium prevents early cytosolic calcium increase and secondary injurious calcium overload in glycolytically inhibited endothelial cells Biochem. Biophys. Res. Commun. 2013; 434:268-272 Crossref Scopus (28) PubMed Google Scholar
  6. [7]7. Senadheera, S. ∙ Kim, Y. ∙ Grayson, T.H. ... Transient receptor potential canonical type 3 channels facilitate endothelium-derived hyperpolarization-mediated resistance artery vasodilator activity Cardiovasc. Res. 2012; 95:439-447 Crossref Scopus (75) PubMed Google Scholar
  7. [8]8. Stoeckli, M. ∙ Chaurand, P. ∙ Hallahan, D.E. ... Imaging mass spectrometry: a new technology for the analysis of protein expression in mammalian tissues Nat. Med. 2001; 7:493-496 Crossref Scopus (1047) PubMed Google Scholar
  8. [9]9. Jones, J.J. ∙ Stump, M.J. ∙ Fleming, R.C. ... Investigation of MALDI-TOF and FT-MS techniques for analysis of Escherichia coli whole cells Anal. Chem. 2003; 75:1340-1347 Crossref Scopus (85) PubMed Google Scholar
  9. [10]10. Jones, J.J. ∙ Stump, M.J. ∙ Fleming, R.C. ... Strategies and data analysis techniques for lipid and phospholipid chemistry elucidation by intact cell MALDI-FTMS J. Am. Soc. Mass Spectrom. 2004; 15:1665-1674 Crossref Scopus (70) PubMed Google Scholar
  10. [11]11. Ho, Y.P. ∙ Fenselau, C. Applications of 1.06-micron IR laser desorption on a Fourier transform mass spectrometer Anal. Chem. 1998; 70:4890-4895 Crossref Scopus (39) PubMed Google Scholar
  11. [12]12. Shanta, S.R. ∙ Choi, C.S. ∙ Lee, J.H. ... Global changes in phospholipids identified by MALDI MS in rats with focal cerebral ischemia J. Lipid Res. 2012; 53:1823-1831 Full Text Full Text (PDF) Scopus (54) PubMed Google Scholar
  12. [13]13. Kobayashi, T. ∙ Nemoto, S. ∙ Ishida, K. ... Involvement of CaM kinase II in the impairment of endothelial function and eNOS activity in aortas of type 2 diabetic rats Clin. Sci. 2012; 123:375-386 Crossref Scopus (32) PubMed Google Scholar
  13. [14]14. Farooqui, A.A. ∙ Horrocks, L.A. ∙ Farooqui, T. Glycerophospholipids in brain: their metabolism, incorporation into membranes, functions, and involvement in neurological disorders Chem. Phys. Lipids. 2000; 106:1-29 Crossref Scopus (392) PubMed Google Scholar
  14. [15]15. Chaurand, P. ∙ Schwartz, S.A. ∙ Reyzer, M.L. ... Imaging mass spectrometry: principles and potentials Toxicol. Pathol. 2005; 33:92-101 Crossref Scopus (149) PubMed Google Scholar
  15. [16]16. Schwamborn, K. ∙ Caprioli, R.M. Molecular imaging by mass spectrometry–looking beyond classical histology Nat. Rev. Cancer. 2010; 10:639-646 Crossref Scopus (298) PubMed Google Scholar
  16. [17]17. Shanta, S.R. ∙ Zhou, L.H. ∙ Park, Y.S. ... Binary matrix for MALDI imaging mass spectrometry of phospholipids in both ion modes Anal. Chem. 2011; 83:1252-1259 Crossref Scopus (88) PubMed Google Scholar
  17. [18]18. Shrivas, K. ∙ Hayasaka, T. ∙ Goto-Inoue, N. ... Ionic matrix for enhanced MALDI imaging mass spectrometry for identification of phospholipids in mouse liver and cerebellum tissue sections Anal. Chem. 2010; 82:8800-8806 Crossref Scopus (52) PubMed Google Scholar
  18. [19]19. Lee, G.K. ∙ Lee, H.S. ∙ Park, Y.S. ... Lipid MALDI profile classifies non-small cell lung cancers according to the histologic type Lung Cancer. 2012; 76:197-203 Full Text Full Text (PDF) Scopus (78) PubMed Google Scholar
  19. [20]20. Kang, S. ∙ Lee, A. ∙ Park, Y.S. ... Alteration in lipid and protein profiles of ovarian cancer: similarity to breast cancer. Int. J. Gynecol. Cancer. 2011; 21:1566-1572 Crossref Scopus (27) PubMed Google Scholar
  20. [21]21. Ching, L.C. ∙ Zhao, J.F. ∙ Su, K.H. ... Activation of transient receptor potential vanilloid 1 decreases endothelial nitric oxide synthase phosphorylation at Thr497 by protein phosphatase 2B-dependent dephosphorylation of protein kinase C Acta Physiol. (Oxf.). 2013; 209:124-135 Crossref Scopus (20) PubMed Google Scholar
  21. [22]22. Kang, H.S. ∙ Lee, S.C. ∙ Park, Y.S. ... Protein and lipid MALDI profiles classify breast cancers according to the intrinsic subtype BMC Cancer. 2011; 11:465 Crossref Scopus (56) PubMed Google Scholar
  22. [23]23. Park, Y.S. ∙ Yoo, C.W. ∙ Lee, S.C. ... Lipid profiles for intrahepatic cholangiocarcinoma identified using matrix-assisted laser desorption/ionization mass spectrometry Clin. Chim. Acta. 2011; 412:1978-1982 Crossref Scopus (22) PubMed Google Scholar
  23. [24]24. Kim, I.C. ∙ Bang, G. ∙ Lee, J.H. ... Low C24-OH and C22-OH sulfatides in human renal cell carcinoma J. Mass Spectrom. 2014; 49:409-416 Crossref Scopus (9) PubMed Google Scholar
  24. [27]27. Malaplate-Armand, C. ∙ Florent-Bechard, S. ∙ Youssef, I. ... Soluble oligomers of amyloid-beta peptide induce neuronal apoptosis by activating a cPLA2-dependent sphingomyelinase-ceramide pathway Neurobiol. Dis. 2006; 23:178-189 Crossref Scopus (180) PubMed Google Scholar
  25. [29]29. Skovgaard, N. ∙ Gouliaev, A. ∙ Aalling, M. ... The role of endogenous H2S in cardiovascular physiology Curr. Pharm. Biotechnol. 2011; 12:1385-1393 Crossref Scopus (73) PubMed Google Scholar
  26. [30]30. Behringer, E.J. ∙ Socha, M.J. ∙ Polo-Parada, L. ... Electrical conduction along endothelial cell tubes from mouse feed arteries: confounding actions of glycyrrhetinic acid derivatives Br. J. Pharmacol. 2012; 166:774-787 Crossref Scopus (51) PubMed Google Scholar
  27. [31]31. Wei, X.N. ∙ Han, B.C. ∙ Zhang, J.X. ... An integrated mathematical model of thrombin-, histamine-, and VEGF-mediated signalling in endothelial permeability BMC Syst. Biol. 2011; 5:112 Crossref Scopus (13) PubMed Google Scholar
  28. [32]32. Liu, B. ∙ Lu, S. ∙ Zheng, S. ... Two distinct phases of calcium signalling under flow Cardiovasc. Res. 2011; 91:124-133 Crossref Scopus (37) PubMed Google Scholar
  29. [33]33. Tran, Q.K. ∙ Ohashi, K. ∙ Watanabe, H. Calcium signalling in endothelial cells Cardiovasc. Res. 2000; 48:13-22 Crossref Scopus (166) PubMed Google Scholar
  30. [34]34. Sundaram, J.R. ∙ Chan, E.S. ∙ Poore, C.P. ... Cdk5/p25-induced cytosolic PLA2-mediated lysophosphatidylcholine production regulates neuroinflammation and triggers neurodegeneration J. Neurosci. 2012; 32:1020-1034 Crossref Scopus (100) PubMed Google Scholar
  31. [35]35. Stephenson, D.T. ∙ Lemere, C.A. ∙ Selkoe, D.J. ... Cytosolic phospholipase A2 (cPLA2) immunoreactivity is elevated in Alzheimer's disease brain Neurobiol. Dis. 1996; 3:51-63 Crossref Scopus (202) PubMed Google Scholar
  32. [36]36. Carter, C.L. ∙ McLeod, C.W. ∙ Bunch, J. Imaging of phospholipids in formalin fixed rat brain sections by matrix assisted laser desorption/ionization mass spectrometry J. Am. Soc. Mass Spectrom. 2011; 22:1991-1998 Crossref Scopus (71) PubMed Google Scholar
  33. [37]37. Farooqui, A.A. ∙ Yang, H.C. ∙ Rosenberger, T.A. ... Phospholipase A2 and its role in brain tissue J. Neurochem. 1997; 69:889-901 Crossref Scopus (313) PubMed Google Scholar
  34. [38]38. Sun, G.Y. ∙ Xu, J. ∙ Jensen, M.D. ... Phospholipase A2 in the central nervous system: implications for neurodegenerative diseases J. Lipid Res. 2004; 45:205-213 Full Text Full Text (PDF) Scopus (351) PubMed Google Scholar
  35. [39]39. Yang, X. ∙ Sheng, W. ∙ He, Y. ... Secretory phospholipase A2 type III enhances alpha-secretase-dependent amyloid precursor protein processing through alterations in membrane fluidity J. Lipid Res. 2010; 51:957-966 Full Text Full Text (PDF) Scopus (30) PubMed Google Scholar
  36. [40]40. Moses, G.S. ∙ Jensen, M.D. ∙ Lue, L.F. ... Secretory PLA2-IIA: a new inflammatory factor for Alzheimer's disease J. Neuroinflammation. 2006; 3:28 Crossref Scopus (125) PubMed Google Scholar
  37. [41]41. van Echten-Deckert, G. ∙ Walter, J. Sphingolipids: critical players in Alzheimer's disease Prog. Lipid Res. 2012; 51:378-393 Crossref Scopus (134) PubMed Google Scholar
  38. [42]42. Jana, A. ∙ Pahan, K. Fibrillar amyloid-beta-activated human astroglia kill primary human neurons via neutral sphingomyelinase: implications for Alzheimer's disease J. Neurosci. 2010; 30:12676-12689 Crossref Scopus (110) PubMed Google Scholar
  39. [43]43. Hannun, Y.A. ∙ Obeid, L.M. Principles of bioactive lipid signalling: lessons from sphingolipids Nat. Rev. Mol. Cell Biol. 2008; 9:139-150 Crossref Scopus (2686) PubMed Google Scholar
  40. [44]44. Jones, E.E. ∙ Dworski, S. ∙ Canals, D. ... On-tissue localization of ceramides and other sphingolipids by MALDI mass spectrometry imaging Anal. Chem. 2014; 86:8303-8311 Crossref Scopus (61) PubMed Google Scholar
  41. [45]45. Ramakrishnan, H. ∙ Hedayati, K.K. ∙ Lullmann-Rauch, R. ... Increasing sulfatide synthesis in myelin-forming cells of arylsulfatase A-deficient mice causes demyelination and neurological symptoms reminiscent of human metachromatic leukodystrophy J. Neurosci. 2007; 27:9482-9490 Crossref Scopus (62) PubMed Google Scholar
  42. [46]46. Irizarry, M.C. A turn of the sulfatide in Alzheimer's disease Ann. Neurol. 2003; 54:7-8 Crossref Scopus (23) PubMed Google Scholar
  43. [47]47. Merrill, J.E. ∙ Murphy, S.P. Inflammatory events at the blood brain barrier: regulation of adhesion molecules, cytokines, and chemokines by reactive nitrogen and oxygen species Brain Behav. Immun. 1997; 11:245-263 Crossref Scopus (107) PubMed Google Scholar
  44. [48]48. Vos, J.P. ∙ Lopes-Cardozo, M. ∙ Gadella, B.M. Metabolic and functional aspects of sulfogalactolipids Biochim. Biophys. Acta. 1994; 1211:125-149 Crossref Scopus (200) PubMed Google Scholar
  45. [49]49. Brun, A. ∙ Englund, E. Brain changes in dementia of Alzheimer's type relevant to new imaging diagnostic methods Prog. Neuropsychopharmacol. Biol. Psychiatry. 1986; 10:297-308 Crossref Scopus (52) PubMed Google Scholar
  46. [50]50. Lassmann, H. ∙ Bancher, C. ∙ Breitschopf, H. ... Cell death in Alzheimer's disease evaluated by DNA fragmentation in situ Acta Neuropathol. 1995; 89:35-41 Crossref Scopus (435) PubMed Google Scholar
  47. [51]51. Han, X. ∙ Holtzman, D.M. ∙ McKeel, Jr, D.W. Plasmalogen deficiency in early Alzheimer's disease subjects and in animal models: molecular characterization using electrospray ionization mass spectrometry J. Neurochem. 2001; 77:1168-1180 Crossref Scopus (433) PubMed Google Scholar
  48. [52]52. Yuki, D. ∙ Sugiura, Y. ∙ Zaima, N. ... Hydroxylated and non-hydroxylated sulfatide are distinctly distributed in the human cerebral cortex Neuroscience. 2011; 193:44-53 Crossref Scopus (53) PubMed Google Scholar
  49. [54]54. Paxinos, G. ∙ Franklin, K.B.J. The Mouse Brain in Stereotaxic Coordinates. 2nd edition. Academic Press, San Diego, CA. 2001; Google Scholar Figures (6) Article metrics Supplementary materials (1) PDF (692.69 KB) Related Articles Advertisement Hide CaptionDownloadSee figure in Article Toggle Thumbstrip Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 Download .PPT Home Access for Developing Countries Articles & Volumes Papers in Press Current Volume List of Volumes For Authors Information for Authors Permissions Submit Manuscript Contact Us Contact Information Journal Info Open Access About the Journal Editorial Board New Content Alerts Special collections Fatty acid metabolism in lipid research Images in Lipid Research Virtual Issues Thematic Reviews Methods Papers Commentaries Patient Oriented Regular Research Articles Other ASBMB Publications Insights in Biochemistry and Molecular Biology Journal of Biological Chemistry Molecular & Cellular Proteomics ASBMB ASBMB ASBMB ASBMB ASBMB ISSN 0022-2275 The content on this site is intended for healthcare professionals. All content on this site: Copyright © 2026 Elsevier Inc., its licensors, and contributors. All rights are reserved, including those for text and data mining, AI training, and similar technologies. For all open access content, the relevant licensing terms apply. Privacy Policy Terms and Conditions Accessibility Help & Contact Responsible AI RELX Thanks for sharing! AddToAny More… We use cookies that are necessary to make our site work. We may also use additional cookies to analyze, improve, and personalize our content and your digital experience. You can manage your cookie preferences using theCookie settings link. For more information, see ourCookie Policy Company Logo Opt-Out Request Honored Cookie Preference Center We use cookies which are necessary to make our site work. We may also use additional cookies to analyse, improve and personalise our content and your digital experience. For more information, see our Cookie Policy and the list of Google Ad-Tech Vendors. You may choose not to allow some types of cookies. However, blocking some types may impact your experience of our site and the services we are able to offer. See the different category headings below to find out more or change your settings. You may also be able to exercise your privacy choices Cookie Settings | Your Privacy Choices as described in our Privacy Policy Manage Consent Preferences Strictly Necessary Cookies Always active These cookies are necessary for the website to function and cannot be switched off in our systems. They are usually only set in response to actions made by you which amount to a request for services, such as setting your privacy preferences, logging in or filling in forms. You can set your browser to block or alert you about these cookies, but some parts of the site will not then work. Functional Cookies These cookies enable the website to provide enhanced functionality and personalisation. They may be set by us or by third party providers whose services we have added to our pages. If you do not allow these cookies then some or all of these services may not function properly. Performance Cookies These cookies allow us to count visits and traffic sources so we can measure and improve the performance of our site. They help us to know which pages are the most and least popular and see how visitors move around the site. Targeting Cookies These cookies may be set through our site by our advertising partners. They may be used by those companies to build a profile of your interests and show you relevant adverts on other sites. If you do not allow these cookies, you will experience less targeted advertising. Cookie List label Consent Leg.Interest label label label Powered by Onetrust

Authors
Hong, J. H., Kang, J. W., Kim, D. K., Baik, S. H., Kim, K. H., Shanta, S. R., Jung, J. H., Mook-Jung, I., & Kim, K. P.
Affiliations
  • Kyung Hee University (KR)
  • Seoul National University (KR)
Corresponding author
Kim, Kwang Pyo
ORCID
Venue
Journal of Lipid Research
Publisher
Elsevier BV
Published
2016-01
Volume
57
Issue
1
Pages
36-45
ISSN
0022-2275 (ISSN-L)
DOI
10.1194/jlr.m057869
PMC
PMC4689334
OpenAlex
W2152378821
Cited by
83
References
54
Citations by year
2026: 6 · 2025: 7 · 2024: 8 · 2023: 6 · 2022: 4 · 2021: 11 · 2020: 10 · 2019: 9 · 2018: 8 · 2017: 9 · 2016: 5
FWCI
5.40
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Lipid Research (publishedVersion, cc-by)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Physical Sciences › Chemistry › Spectroscopy › Mass Spectrometry Techniques and Applications
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolomics and Mass Spectrometry Studies
Keywords
Alzheimer's disease, phospholipids, lipid distribution, MALDI mass spectrometry imaging, 5xFAD mice, amyloid-beta, frontal cortex, hippocampus, subiculum, brain lipids
MeSH terms
Alzheimer Disease, Animals, Brain, Disease Models, Animal, Hippocampus, Humans, Mice, Transgenic, Phospholipids, Amyloid beta-Peptides, Amyloid beta-Protein Precursor, Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization, Mice, Presenilin-1

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review